Yourlawyer.com (Neurontin News)

Pfizer Influenced Neurontin Studies

Thu, 12 Nov 2009 00:00:00 -0800

It has been known that Neurontin is associated with a significant—80 percent, accoring to a prior LA Times report—increase in suicidal ideation and actions. Now, Reuters, is reporting that internal Pfizer Inc. documents point to the drug maker having “altered or omitted unfavorable study findings to expand its epilepsy drug, Neurontin's, market,” citing U.S. researchers looking into how drug manufacturers massage research data. Pfizer is considered, said Reuters, the world’s largest drug maker.

The research found that although clinical trials respond to a specific scientific question, when looking at Pfizer documents and published studies on Neurontin for nonepilepsy conditions, it seems that nearly half—eight of 20—of the studies did not receive medical journal publication, said Reuters. Also, eight of 12 studies that were published, were published with a significant change: Pfizer changed The main scientific question.

"There were a lot of primary outcomes that were shifted around between the planning of the protocol and the reporting of the study," said Kay Dickersin of Johns Hopkins University in Baltimore, quoted Reuters. Dickersin’s study appears in the New England Journal of Medicine. "Some primary outcomes were lost altogether. Some were brand new. Some were secondary outcomes that were upgraded to primary," Dickersin said in a telephone interview with Reuters.

The drug giant funded all of the studies and all showed how Neurontin worked off-label for migraines or pain. Once approved, any drug can be prescribed off-label; however, drug makers are not permitted to market medications for off-label uses and can only tout drugs for Food & Drug Administration (FDA)-approved uses, explained Reuters. Interestingly, drug companies can distribute study reprints from medical journals; of note given the change in focus in a number of such pieces made by Pfizer.

In 2004, Pfizer paid a whopping $430 million to settle a lawsuit over how it illegally promoted Neurontin and was sued last year for off-label marketing, neglecting to release negative study results, and changing the focus of trials to present more favorable outcomes, said Reuters. The 2004 charges stemmed from a federal whistleblower lawsuit that claimed Neurontin marketing was promoting off-label uses, including the treatment of pain and bipolar disorder.

The FDA approved Neurontin in 1983 to treat partial complex seizures. The drug quickly became a blockbuster; by 2004, sales reached $3 billion annually. Neurontin was made by Parke-Davis, a division of Warner-Lambert, which was acquired by Pfizer in 2000.

The family of Susan Bulger filed the first Neurontin suicide lawsuit; Bulger (39) took the drug before hanging herself in 2004. The lawsuit alleged the company hid the drug’s suicide risks. The plaintiffs’ case focused on last December’s decision by the FDA to order all makers of epilepsy drugs to add a suicide-risk warning to their label. As we reported at the time, the new warnings resulted from the FDA’s review of 199 clinical trials of 11 anti-epileptic drugs which showed that patients receiving anti=epileptic drugs had a nearly two-fold risk of suicidal behavior or thoughts (0.43 percent) compared to patients receiving a placebo (0.24 percent). This difference was about one additional case of suicidal thoughts or behaviors for every 500 patients treated with anti-epileptic drugs instead of placebo, the agency said.

Neurontin Suicide Trial to Start Next Week

Fri, 24 Jul 2009 00:00:00 -0700

The first Neurontin suicide lawsuit is set to go to trial. According to a report on Bloomberg.com, about 1200 similar Neurontin lawsuits are pending.

Neurontin was approved by the U.S. Food & Drug Administration (FDA) in 1983 to treat partial complex seizures. The drug quickly became a blockbuster, and by 2004, sales reached $3 billion per year. Neurontin was made by Parke-Davis, a division of Warner-Lambert, which was acquired by Pfizer in 2000.

The first Neurontin lawsuit will begin July 27. According to Bloomberg.com, the lawsuit was filed by the family of Susan Bulger, 39, who took the drug before hanging herself in 2004.

The lawyer representing Bulger's family said he will expose Pfizer’s “seedy” handling of Neurontin during the trial, Bloomberg.com said. The lawsuit alleges the company hid the drug's suicide risks. The plaintiffs' case will focus on last December's decision by the FDA to order all makers of epilepsy drugs to add a suicide-risk warning to their label.

As we reported at the time, the new warnings resulted from the FDA’s review of 199 clinical trials of 11 antiepileptic drugs which showed that patients receiving antiepileptic drugs had almost twice the risk of suicidal behavior or thoughts (0.43 percent) compared to patients receiving a placebo (0.24 percent). This difference was about one additional case of suicidal thoughts or behaviors for every 500 patients treated with antiepileptic drugs instead of placebo, the agency said.

According to Bloomberg.com, the lawsuit claims Bulger was taking Neurontin to treat epilepsy, as well as mood swings and arthritis pain. The promotion of off-label uses of Neurontin played a role in Bulger being prescribed the drug, her family's lawyer maintains. While doctors may prescribe an approved drug in any way they see fit, drug makers may not promote off-label uses.

As we reported previously, in 2004 Warner-Lambert pled guilty and agreed to pay $430 million to resolve charges that it had illegally promoted the off-label use of Neurontin. The charges stemmed from a federal whistleblower lawsuit that had claimed Neurontin marketing was promoting off-label uses, including the treatment of pain and bipolar disorder.

Illegal Marketing of Neurontin Detailed

Thu, 08 Jan 2009 00:00:00 -0800

An article detailing the marketing of Neurontin recently published in the New England Journal of Medicine (NEJM) sheds new light on the tactics used by drug makers to increase sales of their products. In the case of Neurontin, these methods were uncovered because they were being used to illegally promote off-label uses of the drug. However, the authors of the NEJM article contend that the same questionable tactics are regularly used to promote approved of uses of drugs.

Neurontin was approved by the U.S. Food & Drug Administration (FDA) in 1983 to treat partial complex seizures. The drug quickly became a blockbuster, and by 2004, sales reached $3 billion per year. Neurontin was made by Parke-Davis, a division of Warner-Lambert, which was acquired by Pfizer in 2000.

In 2004, Warner-Lambert pled guilty and agreed to pay $430 million to resolve charges that it had illegally promoted the off-label use of Neurontin. The charges stemmed from a federal whistleblower lawsuit that had claimed Neurontin marketing was promoting off-label uses, including the treatment of pain and bipolar disorder. While doctors are free to use approved drugs in anyway they see fit, promoting off-label uses (those not yet approved by the FDA) is illegal.

According to the NEJM, the case that prompted Warner-Lambert's guilty plea made a treasure trove of corporate documents public. They revealed that the Neurontin marketing strategy had two prongs. The first included the promotion of the drug among high prescribing physicians, as well as the cultivation of so-called "thought leaders" - highly-regarded physicians and researchers whose opinions can influence other doctors.

This strategy involved recruiting physicians to talk up the off-label uses of Neurontin to their peers, something known as "peer-to-peer" selling. The NEJM article also says that academic leaders were plied with educational and research grants, as well as lucrative speaking opportunities, to encourage them to promote Neurontin. Many were also invited to be part of "advisory boards" or paid as "consultants" so the drug maker could "cultivate relationships with them and deliver a 'hard hitting message about Neurontin'".

The drug maker also produced or funded education, publications and research that promoted Neurontin, but whose promotional intent was disguised, the NEJM said. For instance Parke-Davis formed speakers bureaus that used "strong Neurontin advocates" to promote the drug. For-profit medical-education companies were given grants to produce "educational" programs to tout off-label use of Neurontin. These same types of companies were also paid to produce articles - under the names of authors chosen by Parke-Davis - that were designed to achieve promotional goals. Research was also designed and commissioned to promote Neurontin, the NEJM said.

The most disturbing aspect of the Neurontin marketing saga is the number of people and institutions needed to pull it off. According to the NEJM, the strategy required the complicity of highly regarded hospitals, universities, researchers and doctors. Even the FDA failed to intervene until the true scope of the promotional program was made public by the whistleblower lawsuit. Until then, the NEJM says, the tactics used to market Neurontin were seen by these individuals and institutions as "business as usual".

While the activities used to promote off-label use of Neurontin may seem shocking, they are hardly unusual. As the NEJM article points out, they only came to light in this case because they were being used to illegally promote non-approved uses of the drug. Similar strategies are often used to promote the approved uses of drugs, but because this marketing is legal, the public never knows.

Epilepsy Drugs to Carry Suicide Warnings

Wed, 17 Dec 2008 00:00:00 -0800

Epilepsy drugs must now carry warnings about their suicide risks, the Food & Drug Administration (FDA) has announced. The drugs subject to the new warning include those used to treat psychiatric disorders, migraine headaches and other conditions, as well as epilepsy. Epilepsy drugs on the list are:

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Clonazepam (marketed as Klonopin)
Clorazepate (marketed as Tranxene)
Divalproex sodium (marketed as Depakote, Depakote ER, Depakene)
Ethosuximide (marketed as Zarontin)
Ethotoin (marketed as Peganone)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Lacosamide (marketed as Vimpat)
Levetiracetam (marketed as Keppra)
Mephenytoin (marketed as Mesantoin)
Methosuximide (marketed as Celontin)
Oxcarbazepine (marketed as Trileptal) Phenytoin (marketed as Dilantin Suspension)
Pregabalin (marketed as Lyrica)
Primidone (marketed as Mysoline)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Trimethadione (marketed as Tridione)
Zonisamide (marketed as Zonegran)

Any available generic versions of these drugs will also carry the new epilepsy drugs, the FDA said.

The FDA said its actions were based on the agency's review of 199 clinical trials of 11 antiepileptic drugs which showed that patients receiving antiepileptic drugs had almost twice the risk of suicidal behavior or thoughts (0.43 percent) compared to patients receiving a placebo (0.24 percent). This difference was about one additional case of suicidal thoughts or behaviors for every 500 patients treated with antiepileptic drugs instead of placebo, the agency said.

Four of the patients who were randomized to receive one of the antiepileptic drugs committed suicide, whereas none of the patients in the placebo group did. Results were insufficient for any conclusion to be drawn about the drugs' effects on completed suicides. The FDA added that the biological reasons for the increase in the risk for suicidal thoughts and behavior observed in patients being treated with antiepileptic drugs are unknown.

In addition to the suicide warning, the FDA is also requiring the drugs' manufacturers to submit f a Risk Evaluation and Mitigation Strategy for each medication , including a Medication Guide for patients. The guides will contain FDA-approved information about the risks of suicidal thoughts and behaviors associated with the class of antiepileptic medications. Medication Guides are manufacturer-developed handouts that are given to patients, their families and caregivers when a medicine is dispensed.

Acting under the authorities of the Food and Drug Administration Amendments Act of 2007 (FDAAA), the FDA is requiring manufacturers of antiepileptic drugs to submit to the agency new labeling within 30 days, or provide a reason why they do not believe such labeling changes are necessary. In cases of non-compliance, FDAAA provides strict timelines for resolving the issue and allows the agency to initiate an enforcement action if necessary.

Pfizer Neurontin Studies Altered, Suppressed to Boost Sales

Wed, 08 Oct 2008 00:00:00 -0700

A lawsuit against Pfizer Inc. claims the drug maker delayed the release and altered the conclusions of Neurontin studies that did not support expanded use of the epilepsy drug. Pfizer is just the latest drug maker accused of manipulating research in this way for marketing purposes. Earlier this year, a Vioxx lawsuit accused Merck & Co. of omitting findings on cardiovascular problems and death rates in studies it funded.

Documents detailing the allegedly-manipulated Neurontin studies were released in a federal lawsuit filed by heath insurers and consumers who want refunds for the money they spent on the drug. They are claiming that Pfizer fraudulently marketed Neurontin. The plaintiffs' petition to have their Neurontin suits consolidated in a class action was rejected by the court last year, but they are trying again.

According to The Wall Street Journal, Pfizer's Warner-Lambert unit pled guilty in 2004 to felony charges that it promoted Neurontin for uses not approved by the Food and Drug Administration, including bipolar disorder and chronic nerve pain. The FDA originally approved the drug to treat epilepsy, and in 2002 it was approved to treat one type of pain related to shingles. Pfizer paid $430 million to resolve the charges and reimburse state Medicaid programs for or off-label uses of Neurontin. At the time, Pfizer said that after it acquired in Warner-Lambert in 2000, it made sure no illegal marketing was being conducted.

But according to documents and emails released in the Neurontin lawsuit in the U.S. District Court in Boston, marketers at Pfizer continued to manipulate studies in order to boost the drug's sales. The studies in question found no beneficial effect from Neurontin for the treatment of conditions other than epilepsy.

According to one 2000 email sent after the company acquired Warner-Lambert, a Pfizer executive suggested that the company delay releasing a European study that showed Neurontin was of little help in treating diabetic nerve pain. "I think we can limit the potential downsides of the ... study by delaying the publication for as long as possible," wrote Michael Rowbothan, then Neurontin's marketing team leader. He added that "it will be more important to how WE write up the study."

In another email, Pfizer's scientific manager on that study wrote she had been instructed "that we should take care not to publish anything that damages Neurontin's marketing success.

In 2002, Neurontin's senior marketing manager, Angela Crespo, wrote an email to an outside firm hired to write-up the European study results: "We are not interested at all in having this paper published because it is negative!!"

According to The Wall Street Journal, Pfizer's write up of the European Neurontin study was ultimately rejected by two medical journals. Court documents show that some of the journals' reviewers thought the articles presented the findings in a too-favorable light.

In the end, no journal ever published that Neurontin study. But Pfizer did eventually summarize its results in a review published in 2003 in the journal Clinical Therapeutics. However, that same review did not make mention of a second Scandinavian study that found Neurontin was no better than a placebo in treating post-operative nerve pain.

The court documents also show that a five-year Spanish study completed in 2004 that investigated Neurontin as a possible treatment for bipolar disorder was altered. Researchers on the study originally found that Neurontin patients did no better than those on a placebo. But by the time it was published in 2006, the study's conclusions had been changed to claim that the results indicated a benefit from Neurontin.

According to the Journal, prior to publication, the lead researcher on the Spanish study had modified the scale used to assess how severely patients exhibited bipolar bipolar disorder. While that change helped boost Neurontin's score in the study, it was never disclosed by the researchers. Making a change like that is considered improper by most scientists, especially when it is not disclosed.

The lead attorney in the Neurontin lawsuits told The Wall Street Journal that Pfizer's manipulation and of the Neurontin studies created the illusion of Neurontin's efficacy in the scientific record" that encouraged doctors to use the drug even when it wasn't effective.

FDA Looking at Suicide Risks of Popular Drugs

Tue, 02 Sep 2008 00:00:00 -0700

It seems that some suicides might be linked to a variety of drugs that are surprising experts. In one case, the Associated Press (AP) reports a 15-year-old high school football player taking the allergy and asthma medication Singular hanged himself. In another, the AP reports that a physician taking Neurontin for an old back injury also hanged himself. The victims’ families believe the drugs, which were prescribed to relieve physical—not psychological—symptoms, upset their family members mental and emotional balance. Now, federal drug regulators are investigating, says the AP.

About two months following the teen’s suicide, Merck & Company—maker of Singulair—revised its prescribing literature to indicate that some patients experienced suicidal thinking and behavior. Merck said that the death could be a coincidence. "Singulair is a really effective drug that has been on the market 10 years and has been taken by millions of patients," said Dr. Alan Ezekowitz, an asthma expert with Merck.

Meanwhile, the 54-year-old doctor began taking Neurontin, an epilepsy drug made by Pfizer, which is also prescribed for nerve-related pain and chronic back trouble. Pfizer said that since Neurontin was first marketed in the 1990s, the prescribing literature listed "suicidal" and "suicidal gesture" as rarely reported adverse events seen in clinical trials. "Based on an extensive review of our clinical trial data for Neurontin, we see no evidence to support the claim that Neurontin causes an increased risk of suicide-related events," Pfizer said. The doctor’s family is suing Pfizer and represents one of about 250 such lawsuits.

The AP reports that just this summer, the US Food and Drug Administration (FDA) “convened a panel of scientific advisers to evaluate the suicide risks of 11 anti-seizure drugs, including Neurontin.” Also, until recently, the FDA focused on psychiatric drugs, such as antidepressants prescribed to youngsters, when looking at medication-related suicide risks. Now, officials “unexpectedly broadened their concerns to include a medication for asthma, drugs for controlling seizures, and even one for quitting smoking,” the AP says. These drugs cover a spectrum of medical conditions not typically linked with psychiatric disorders.

Some independent experts are now seeing a gap in the FDA's knowledge of how drugs affect the brain, says the AP, and that “even if medications are intended for physical conditions, some drugs can have unforeseen consequences if they are able to enter the brain.” A Columbia University research group developed a method for collecting and assessing information about suicidal thinking and behavior among those enrolled in drug trials. The information is used to measure a medication’s suicide risks, possibly helping identify such risks before a drug goes to market. Although the FDA helped fund the research, it does not require drug makers to utilize the system and only requires such assessments on a case-by-case basis.

"Even though a drug is identified as a drug for weight control, or smoking cessation, or asthma, these drugs often also get into the brain, so there is always the potential for having psychiatric side effects," said Dr. Thomas Laughren, head of the FDA's division of psychiatric products. "But we don't have any unifying hypothesis as to why very different classes of drugs have psychiatric side effects."

Epilepsy Drugs Targeted for Black Box Suicide Warning

Tue, 08 Jul 2008 00:00:00 -0700

Federal regulators want the makers of epilepsy drugs to add a black box warning to their labels about their association with suicidal thoughts and behavior. The Food & Drug Administration (FDA) is set to ask an outside advisory panel for its recommendations on the proposed black box at a meeting this Thursday.

In total, 11 epilepsy drugs could get the new black box warning - the FDA's strongest safety notice. They include:

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

The FDA began investigating if epilepsy drugs posed any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. The studies tracked almost 28,000 people given epilepsy medications and another 16,000 given dummy pills.

According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. For every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo.

According to the FDA, three of the 11 drugs studied showed no clear signal of suicidal problems. However, the agency is still leaning towards including the warning on all the drugs, as sample sizes in some of the studies might have been too small to accurately assess suicide risks. One of the issues the agency will ask the panel to address at Thursday's meeting is whether all of the drugs, or just some of them, should be subjected to the black box.

The FDA is not bound to follow the recommendations of its advisory panels, but it usually does so.

Neurontin Should Have Had Depression Warning, Neurologist Says

Fri, 20 Jun 2008 00:00:00 -0700

A British neurologist says he advised the maker of Neurontin to include a warning on its label about its potential to cause depression and aggression, but he was ignored. According to The Wall Street Journal, the neurologist, Michael R. Trimble from the University of London, was testifying at a hearing to decide whether civil cases brought against Pfizer alleging suicides linked to Neurontin can proceed.

Neurontin was approved for sale in the mid-1990s as a treatment for epileptic seizures. While Neurontin is approved for the treatment of epilepsy, it has been used "off-label" to treat a wide range of other conditions, including bipolar disorder, ADHD and Migraines.

Earlier this month, the U.S. Food & Drug Administration (FDA) directed the makers of 11 epilepsy drugs, including Neurontin, to add new warnings to their labels about the drugs' potential to cause suicidal thoughts and behavior. The FDA began investigating if epilepsy drugs posed any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. The studies tracked almost 28,000 people given epilepsy medications and another 16,000 given dummy pills.

According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. For every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo.

According to The Wall Street Journal, Dr. Trimble testified that in 1995 and 1996, he was hired to write two confidential reports for Parke-Davis -- now a unit of Pfizer -- because the company "was concerned about psychosis" as a potential side effect of Neurontin. Dr. Trimble said he was unable to find a link to psychosis, but did find one between the drug and depression and aggression. For the 1996 report, Dr. Trimble analyzed nine patients who had no previous symptoms of the side effects. Five of those patients exhibited depression and aggression after they had begun taking Neurontin. Dr. Trimble said he recommended to the company that the drug "should carry some kind of warning" for susceptible patients.

Dr. Trimble's testimony was part of a hearing that was jointly held by judges for U.S. District Court in Boston and a New York state court who are hearing similar cases. According to The Wall Street Journal, various lawsuits have been consolidated in the federal court in which plaintiffs allege more than 100 suicides were connected to Neurontin usage.

Epilepsy Drugs to Get Suicide Warnings, FDA Confirms

Fri, 06 Jun 2008 00:00:00 -0700

US regulators are very close to finalizing new suicide warnings for 11 epilepsy drugs, The Wall Street Journal reported today. This past January, the Food & Drug Administration (FDA) issued an Early Communication announcing a safety review of the epilepsy drugs after a study showed they increased patients' risk of suicidal thoughts and behavior.

The 11 epilepsy drugs slated for a new suicide warning are:

Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
Felbamate (marketed as Felbatol)
Gabapentin (marketed as Neurontin)
Lamotrigine (marketed as Lamictal)
Levetiracetam (marketed as Keppra)
Oxcarbazepine (marketed as Trileptal)
Pregabalin (marketed as Lyrica)
Tiagabine (marketed as Gabitril)
Topiramate (marketed as Topamax)
Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
Zonisamide (marketed as Zonegran)

In addition to treating epilepsy, the anti-seizure medications are used for a variety of other illnesses, including migraines, certain nerve-pain disorders, and psychiatric diseases such as bipolar disorder that themselves carry a risk of suicide.

According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. For every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo.

In an interview with The Wall Street Journal, Russell Katz, director the FDA's neuropharmacological drug division confirmed the suicide warnings are coming. "We are working on the labeling changes that we want to get to the companies," he said. An FDA advisory panel is slated to take up the issue of epilepsy drugs and suicide on July 10, but the Journal speculated the new warnings could come even sooner than that.

At least one drug maker, Pfizer Inc., is less than pleased at this development. Pfizer disputed the FDA's analysis in a forum this week sponsored by the Epilepsy Study Consortium in New York. Pfizer especially disputes the inclusion of Lyrica - one of the company's biggest growth drivers -on the FDA's warning list. Pfizer said that Lyrica accounted for only 6.3% of the total 142 suicidal events cited by the FDA analysis. But the FDA is sticking to its guns, and the new suicide warning will apply to all 11 epilepsy drugs.

Most other epilepsy drug makers are resigned to the label changes, according to the Journal. GlaxoSmithKline, the maker of Lamictal, approached the FDA this year to volunteer changes regarding possible suicidal-behavior risks. Other drug makers may have chosen not to challenge the FDA on suicide warnings because their medications are no longer as lucrative as they once were, as patents on many epilepsy drugs have, or are close to, expiring.

Epilepsy Drugs Double Suicide Risks, FDA Warns

Sat, 02 Feb 2008 00:00:00 -0800

Epilepsy drugs have been linked to a increased risk of suicidal thoughts and behavior, the Food & Drug Administration (FDA) warned this week. According to an FDA analysis, people taking antiepileptic drugs are twice as likely to experience suicidal thoughts or behavior than those taking placebo.

The FDA began investigating if epilepsy drugs pose any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. The antiepileptic medications studied by the FDA included:

•   Carbamazepine(marketed as Carbatrol, Equetro, Tegretol, Tegretol XR)
•   Felbamate (marketed as Felbatol)
•   Gabapentin (marketed as Neurontin)
•   Lamotrigine (marketed as Lamictal)
•   Levetiracetam (marketed as Keppra)
•   Oxcarbazepine (marketed as Trileptal)
•   Pregabalin (marketed as Lyrica)
•   Tiagabine (marketed as Gabitril)
•   Topiramate (marketed as Topamax)
•   Valproate (marketed as Depakote, Depakote ER, Depakene, Depacon)
•   Zonisamide (marketed as Zonegran)

The studies tracked almost 28,000 people given the medications and another 16,000 given dummy pills. According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. There was no clear pattern of risk across age groups.

Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. According to the FDA for every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo. Even though the FDA only looked at 11 epilepsy medications, the agency said the suicide warning applied to all epilepsy drugs.

Millions of people take epilepsy drugs. Such anti-seizure medications are used for a variety of illnesses in addition to epilepsy, including migraines, certain nerve-pain disorders, and psychiatric diseases such as bipolar disorder that themselves carry a risk of suicide.

Doctors and other healthcare providers where advised by the FDA to balance the risk for suicidal thoughts and behavior with the clinical need for the drug and to be aware of the possibility of the emergence or worsening of depression, suicidality, or any unusual changes in behavior. Healthcare providers where told to inform patients, their families, and caregivers of the potential for an increase in the risk of suicidality so they are aware and able to notify their healthcare provider of any unusual behavioral changes.

Because skipping epilepsy medication can result in seizures, the FDA said that patients should ask a doctor before making medication changes. The FDA said patients and their families should pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences. Patients and their families should be aware of common warning signs that might be a signal for risk of suicide, inlcuidng talking or thinking about wanting to hurt themselves or end their lives; withdrawing from friends and family; Becoming depressed or having depression get worse; becoming preoccupied with death and dying; and giving away prized possessions. If these or any new and worrisome behaviors occur, patients or their families should contact the responsible healthcare professional immediately.

The FDA said it would be working with manufacturers of marketed epilepsyc drugs to include this new information about suicide risks in the labeling for these products. The agency anticipates that labeling changes will be applied broadly to the entire class of drugs. The FDA is also planning to discuss the suicide data at an upcoming advisory committee meeting.

Epilepsy Drugs Linked to Suicide

Fri, 01 Feb 2008 00:00:00 -0800

Epilepsy drugs, including Pfizer Inc.'s Neurontin, Novartis AG's Tegretol and Abbott Laboratories' Depakote, have been linked to an increased risk of suicidal thoughts and behavior, the Food & Drug Administration (FDA) warned yesterday. According to an FDA analysis, people taking epilepsy drugs are twice as likely to experience suicidal thoughts or behavior as those taking placebo.

Millions of people take epilepsy drugs. Such anti-seizure medications are used for a variety of illnesses in addition to epilepsy, including migraines, certain nerve-pain disorders, and psychiatric diseases such as bipolar disorder that themselves carry a risk of suicide.

The FDA began investigating if epilepsy drugs pose any suicide risk in 2005. In doing so, the FDA analyzed almost 200 studies of 11 anti-seizure drugs, some that have been on the market for decades. The studies tracked almost 28,000 people given the medications and another 16,000 given dummy pills. According to the FDA, 0.43 percent of drug-treated patients experienced suicidal thoughts or behavior, compared with 0.22 percent of placebo-takers. The higher risk of suicidal thoughts and behaviors was observed at one week after starting a drug and continued to at least 24 weeks. The results were generally consistent among all the different drug products studied and were seen in all demographic subgroups. There was no clear pattern of risk across age groups.

Overall, four people in the drug-treated groups committed suicide, and none in the placebo groups. According to the FDA for every 1,000 patients, about two more patients taking epilepsy drugs experienced suicidal thoughts than those who took placebo. Even though the FDA only looked at 11 epilepsy medications, the agency said the suicide warning applied to all epilepsy drugs.

Doctors and other healthcare providers where advised by the FDA to balance the risk for suicidal thoughts and behavior with the clinical need for the drug and to be aware of the possibility of the emergence or worsening of depression, suicidality, or any unusual changes in behavior. Healthcare providers where told to inform patients, their families, and caregivers of the potential for an increase in the risk of suicidality so they are aware and able to notify their healthcare provider of any unusual behavioral changes.

Because skipping epilepsy medication can result in seizures, the FDA said that patients should ask a doctor before making medication changes. The FDA said patients and their families should pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences. Patients and their families should be aware of common warning signs that might be a signal for risk of suicide, including talking or thinking about wanting to hurt themselves or end their lives; withdrawing from friends and family; becoming depressed or having depression get worse; becoming preoccupied with death and dying; and giving away prized possessions. If these or any new and worrisome behaviors occur, patients or their families should contact the responsible healthcare professional immediately.

The FDA said it would be working with manufacturers of marketed epilepsy drugs to include this new information about suicide risks in the labeling for these products. The agency anticipates that labeling changes will be applied broadly to the entire class of drugs. The FDA is also planning to discuss the suicide data at an upcoming advisory committee meeting.

More drugs get slapped with lawsuits

Wed, 23 Aug 2006 00:00:00 -0700

A new batch of drugs faces a barrage of lawsuits claiming that the drugs injured users and that manufacturers are to blame.

More than 6,000 lawsuits have been filed in recent years against four drugs taken by millions of patients: hormone-replacement drug Prempro, birth-control patch Ortho Evra, anti-psychotic Seroquel and anti-seizure drug Neurontin.

The plaintiffs claim drugmakers failed to disclose the drugs' risks or failed to properly test them, or both. The claims are similar to those against Merck's painkiller Vioxx, which faces 14,000 lawsuits. Unlike Vioxx, these drugs are still being sold, and the Food and Drug Administration considers their benefits worth their risks.

The first trials have begun or are near for Prempro and Neurontin. Johnson & Johnson has started settling some Ortho Evra cases, plaintiffs' lawyers say.

The lawsuits raise questions about whether drugmakers and the FDA pay ample attention to patient safety. Since 2000, more than 65,000 product liability lawsuits have been filed against prescription drugmakers, the most of any industry, says researcher Thomson West.

The pace isn't likely to slow, given the number of drugs on the market, the millions of consumers taking them and the skill of plaintiffs' lawyers in finding consumers who suffered adverse reactions, says professor Lars Noah of the University of Florida College of Law.

"The lawyers have created almost an assembly-line approach to use against an industry that's in tobacco-land in terms of how much people hate it," Noah says.

Drugmaker Wyeth faces more than 5,000 cases for Prempro and Premarin, hormone-replacement drugs for menopausal symptoms. The first trial started Monday in Little Rock. Plaintiff Linda Reeves alleges she developed breast cancer as a result of taking the drugs from 1983 through 2000. Breast cancer accounts for the majority of claims.

Wyeth and plaintiffs' lawyers refused comment, citing a judge's gag order. Wyeth has said it did nothing wrong and that the drugs' warnings reflected available scientific data and FDA requirements.

A study halted in 2002, the Women's Health Initiative, found that Prempro patients had a higher risk of breast cancer, stroke and heart disease. Later that year, Wyeth added a boldface warning on Prempro, which combines estrogen and progestin, and on Premarin, an estrogen, regarding the study.

In 2003, the warnings were put in a box, making them more prominent. The drugs' combined sales fell to $909 billion last year from $2 billion in 2001.

In March, Wyeth won the first state case when a New York judge issued a summary judgment, saying the drugs' warnings were adequate. The case is being appealed, the plaintiff's lawyer says.

Wyeth's exposure is not likely to be nearly as large as the $21 billion it's paying to settle tens of thousands of claims over former diet drug fen-phen, linked to heart and lung problems. Not only are there fewer cases, but also it's difficult to prove that a drug caused someone's cancer a key hurdle in most drug lawsuits, Noah says.

A Neurontin plaintiffs' lawyer has advocated that the FDA require a black-box suicide warning on Neurontin, which has been taken by more than 10 million people and is widely prescribed for pain and bipolar sufferers. Drugmaker Pfizer says there's no scientific evidence linking Neurontin and suicide.

In December, Pfizer changed Neurontin's label to list "suicide" and "suicide attempt" as infrequent adverse events as opposed to "suicide gesture" as a rarer event. Pfizer says it made the change because of adverse event reports filed to the FDA. The reports do not prove a drug was to blame.

Warning raised

In the Ortho Evra birth-control patch cases, plaintiffs allege that the company failed to adequately test the patch's safety. Many of the women claim they suffered blood clots as a result of using it.

"The plaintiffs tend to be younger women, and you don't normally see strokes or blood clots in that population," Noah says.

The FDA last year required a warning on the patch, saying users will be exposed to 60% more estrogen than with typical birth-control pills. The warning came after the FDA and the drugmaker compared estrogen levels for the patch vs. pills. The FDA also said increased estrogen may raise the risk of clots.

When the FDA approved the patch in 2001, however, an FDA approval document said the risks were "similar to the risks of using birth-control pills."

The patch delivers more estrogen into the bloodstream. With pills, some estrogen is lost in the digestive tract.

Ortho-McNeil Pharmaceutical, and parent Johnson & Johnson, refused to comment specifically on the lawsuit allegations. In a general statement, it said that more than 5 million women have used the patch and that, when used as labeled, it is safe.

Settlements' cost

Last year, drugmaker Eli Lilly took a $1 billion charge to settle about 10,500 lawsuits claiming anti-psychotic Zyprexa caused diabetes or high blood glucose.

Similar claims have been made against AstraZeneca Pharmaceuticals' Seroquel, the No. 1 anti-psychotic, with more than 16 million users since its 1997 launch. Plaintiffs' lawyers claim AstraZeneca downplayed the diabetes risks and hid important safety information from the FDA.

AstraZeneca is confident in the drug and plans to defend itself, says spokesman Jim Minnick. He says the same lawyers who filed suit against Zyprexa are coming after Seroquel hoping for a similar result a charge plaintiffs' lawyers deny.

Lawsuits' effects

Professor Noah says the threat of litigation will do little to stop companies from pursuing future drugs with such big markets.

Seroquel had 2005 sales of $2.8 billion. Neurontin, pre-generic competition, also posted annual sales in excess of $2 billion, as did the hormone-replacement drugs.

But Lisa Rickard, president of the U.S. Chamber Institute for Legal Reform, says litigation costs not only eat into research funds but change consumer behaviors. She cites a 2003 Harris Poll, commissioned by her group, that found that almost four out of 10 doctors had patients stop taking necessary medications after they heard a drug was involved in a liability lawsuit.

She says plaintiffs' lawyers jam courts with so many lawsuits, many frivolous, that firms settle to avoid the expense and uncertainty of fighting them. "The situation has gotten out of hand," says Rickard, whose group is affiliated with the U.S. Chamber of Commerce.

According to one attorney, law firms stand to lose $3 million to $5 million by bringing drugmakers to trial and don't pursue frivolous cases. "If a product hurts enough people, it gets the attention of the lawyers."

Pfizer Recalls Epilepsy Drug

Sat, 23 Apr 2005 00:00:00 -0700

Pfizer Inc. has voluntarily recalled 40,000 bottles of its Neurontin epilepsy medication after a manufacturing malfunction caused some of the bottles to contain either empty or partially filled capsules.

Pfizer said it is possible that patients taking Neurontin to control their epilepsy could experience seizures from a missed dose of the product from one of the empty or partially filled capsules.

Pfizer said Friday that only 100-milligram capsules were affected from a specific lot 15224V distributed in October and November of this past year. Pfizer initially notified pharmacists and its distributors of the recall on Feb. 23. The company issued a press release on Friday as a follow-up to its initial recall.

The New York-based Pfizer, which employs about 6,500 in southeastern Connecticut, also encouraged pharmacists to immediately contact any of their customers using Neurontin to ensure their full awareness of the problem with the one lot of drugs that was distributed only in the United States.

Pfizer officials have been working closely with federal Food and Drug Administration officials throughout the recall process. The company said patients should not stop taking Neurontin before consulting with their physicians.

Neurontin has been approved by the FDA for treatment of partial seizures in adults and children and the drug also is approved for management of the pain that can last one to three months after a patient has shingles. The drug is available in various dosage forms, including tablets, capsules and liquid. During the first quarter of this year, Pfizer said the drug had worldwide sales of $182 million, down significantly from its first-quarter sales in 2004 of $696 million. The drug is one of several Pfizer drugs that have lost their patent exclusivity and now face increasing generic competition.

Pfizer said patients should contact their pharmacists if they believe their prescription for Neurontin was filled between Oct. 1, 2004 and March 15, 2005. In addition, consumers with questions about the recall should call Pfizer at 1-800-438-1985. Pfizer said the recall of the 40,000 bottles of Neurontin would not result in any shortages for the central-nervous system drug.

F.D.A. Is Looking Into Epilepsy Drugs

Fri, 22 Apr 2005 00:00:00 -0700

The Food and Drug Administration has begun a preliminary inquiry into whether epilepsy drugs may increase the risk of suicidal behavior in some patients, particularly those who use them for psychiatric illnesses.

Prompted in part by a lawyer's claims against a leading anticonvulsant, Neurontin, the F.D.A. asked makers of all epilepsy medicines last month to reanalyze research to see if there was evidence of increased suicide risk.

"I don't think we have any suspicion yet that these drugs actually do that," said Dr. Robert Temple, the F.D.A.'s drug policy chief.

Antiseizure drugs are becoming widely used to treat some psychiatric illnesses as well as pain.

FDA Looks For Suicide Risks Among Epilepsy Drug Users

Thu, 21 Apr 2005 00:00:00 -0700

The Food and Drug Administration has begun a preliminary inquiry into whether epilepsy drugs might increase the risk of suicidal behavior in some patients, particularly those who use them for psychiatric illnesses instead of seizure prevention.

Prompted in part by an attorney's claims against the leading anti-convulsant, Neurontin, the FDA last month asked makers of all epilepsy medicines to reanalyze research studies done with the drugs to see if there's any evidence of increased suicide risk.

"I don't think we have any suspicion yet that these drugs actually do that," cautioned Dr. Robert Temple, the FDA's drug policy chief.

It's the same type of analysis that the FDA last year ordered for anti-depressants amid controversy over their use by children and teenagers. Ultimately, those drugs were linked to an increase in suicidal thoughts and actions in a small fraction of young patients.

In addition to use by millions of people with epilepsy, anti-seizure drugs are becoming widely used to treat psychiatric illnesses such as bipolar disorder also called manic depression as well as pain and other conditions. Some epilepsy drugs have FDA approval for various other uses, while others are prescribed "off-label."

A New York attorney last summer filed a petition with the FDA asking that a black-box warning the FDA's toughest about suicide be placed on Neurontin's label. In the petition, Finkelstein cited 25 reports of suicides among Neurontin users from the FDA's own database. The FDA is still investigating the petition.

Pfizer will comply with the FDA's request to reanalyze its studies, but patient data already submitted to the agency "shows no link between Neurontin and suicidal thoughts or behavior," said spokesman Paul Fitzhenry.

FDA Checks Into Possibility of Epilepsy Drug-suicide Link

Wed, 20 Apr 2005 00:00:00 -0700

The Food and Drug Administration wants 14 drugmakers to check their study data to see if use of epilepsy drugs results in suicidal behavior or thoughts.

The FDA requested the reviews last month and gave the drugmakers six months to respond.

The request is similar to one the FDA made in 2003 regarding antidepressants and suicidal behavior in children. That review resulted in a "black box" warning, the FDA's toughest, on the drugs' labels last year. This is only the second review of that type, says Robert Temple of the FDA's Center for Drug Evaluation and Research.

U.S. sales of anti-seizure drugs, including No. 1-seller Neurontin, made by Pfizer, and No. 2 Topamax from Ortho-McNeil Pharmaceutical, were the fifth-largest drug category last year, says research firm IMS Health. That's largely because they're used for many ailments other than epilepsy, which affects an estimated 2.7 million Americans. Neurontin is most often prescribed for pain. Topamax also prevents migraines.

The FDA says it's doing the review because, as it learned with antidepressants, links between medications and adverse events can be missed "if you don't look properly," Temple says. The FDA review was first reported by the Boston Globe Wednesday.

The agency also has been pressed by New York law firm Finkelstein & Partners. It asked the FDA last year to add a black box suicide warning to Neurontin and says it has given the FDA 261 reports of people who committed suicide while on Neurontin. None had attempted suicide before, says attorney Andrew Finkelstein. Half took Neurontin for pain, he says.

Finkelstein has filed 73 personal injury lawsuits against Pfizer regarding Neurontin. Finkelstein says FDA drug reviewers in 1992 two years before Neurontin hit the market concluded the drug's safety profile was good, but that less common, serious adverse events would limit its usefulness. One concern was that depression in people with epilepsy might worsen and lead to suicide. The FDA is reviewing that report, Temple says.

More than 10 million people have taken Neurontin, Pfizer says. The drug's prescribing information, a 29-page document that goes to doctors, mentions "suicide gesture" as a rare adverse event, meaning it occurs in fewer than 1% of 1,000 patients. Pfizer spokesman Paul Fitzhenry says Neurontin adverse event reports over the past decade "show no link between Neurontin and suicidal thoughts or behavior."

Last year, Pfizer division Warner-Lambert pleaded guilty to illegally marketing Neurontin to treat ailments for which it was not FDA approved. Although the marketing occurred in the mid-1990s, before Pfizer owned Warner, Pfizer paid $430 million in fines to settle the Justice Department's allegations.

Neurontin is FDA-approved to treat epilepsy when used with another drug and for pain related to shingles. But doctors can prescribe drugs for whatever they want, and prosecutors say the illegal promotion boosted Neurontin sales so that 94% were for non-FDA approved conditions by 2002.

Gregory Barkley, an epilepsy specialist at Henry Ford Hospital in Detroit, says he would not be surprised if the review shows high rates of suicidal behavior. People with epilepsy have about twice the rate of depression as the general population, he says, and depression rates are also high among bipolar patients, who may take anti-convulsants. "I doubt that one anti-convulsant will be any worse than others," he says.

Neurontin sales fell 74% in the first quarter to $182 million because of new generic competition.

`Snake Oil' Subject of Suit

Fri, 24 Dec 2004 00:00:00 -0800

Dan Allen was diagnosed three years ago with a mysterious neurological disorder that put him in a wheelchair, suffering from headaches, nausea, dizziness and memory loss.

Among other medications, the former Holy Cross football coach was given Neurontin, an epilepsy treatment widely prescribed for everything from pain relief to insomnia to depression.

But Allen's widow, Laura, 49, uses different words to describe Neurontin:

``It was snake oil,'' she said yesterday in an exclusive interview with the Herald.

Allen will appear as a named complainant in a proposed class-action suit against Pfizer Inc., the manufacturer of Neurontin, the Herald has learned.

The suit is expected to be filed Monday in Suffolk Superior Court.

Brought on behalf of nearly 1,000 people statewide, the suit alleges that Pfizer broke the ``Pfizer basically sold a sugar pill, saying it was good medicine,'' said Robert Bonsignore, a local consumer activist and lawyer who will file the suit.

Pfizer spokesman Paul Fitzhenry acknowledged that the company is the target of a number of class-action complaints that mirror parts of a successful whistleblower case brought by the federal government.

Last May, Pfizer paid $240 million in criminal fines as part of a $430 million settlement for illegally promoting so-called ``off-label'' uses for Neurontin.

``These suits closely track those allegations,'' said Fitzhenry. ``We do not believe efforts to certify (them) as class-action are supported by the law. They hinge on the doctor-patient relationship.''

The whistleblower case was set off by a onetime medical liaison with Parke-Davis Inc., which was later acquired by Pfizer.

The company was found to have urged its medical liaisons, or salespeople, to provide doctors with misleading and even wrong information about Neurontin. The doctors, in turn, prescribed it for a host of ailments the drug hadn't been approved to treat.

By law, doctors can prescribe medicines for uses other than those approved by the U.S. Food and Drug Administration. But drug companies can't promote those uses.

Dan Allen died at age 48 last May from multiple chemical sensitivity, which is thought to have been triggered by hazardous substances used in refinishing a gymnasium floor at Holy Cross.

Laura Allen, the mother of three, ages 11 to 19, sees the tragedy that befell her husband as a series of wrongs she is now trying to put right.

She has sued the contractors who refurbished the Worcester college's field house. Now Allen is adding her name to the suit against Pfizer.

``This is the beginning of a long string of things that need to be investigated,'' she said.

Drugmaker Admitted Fraud, But Sales Flourish

Mon, 16 Aug 2004 00:00:00 -0700

What happens to drug companies that commit federal crimes? For the nation's No. 1 drug company, the answer is: some pain, more gain.

In mid-May, Pfizer's (PFE) Warner-Lambert division pleaded guilty to illegally marketing a drug called Neurontin to treat ailments for which it was not approved. Pfizer, which did not own Warner-Lambert when the government said the wrongdoing happened, paid a $430 million fine to settle charges that included defrauding Medicaid.

Pfizer's confession that the success of one of its top drugs was built partly on fraud may have been humbling, but it isn't hurting the bottom line. Neurontin sales last quarter rose 32% from a year ago, and 2004 sales should pass last year's $2.7 billion. With few exceptions, state Medicaid programs pay for Neurontin just as before and so do major insurers.

The tale of Neurontin shows how hard it is to stop the momentum of a blockbuster drug, absent evidence that it is unsafe, and to control health care costs.

"They (Warner-Lambert) made their money, and they got off cheap," says Larry Sasich, a doctor of pharmacy at the consumer-oriented Public Citizen Health Research Group based in Washington, D.C. Without prosecution of Warner-Lambert executives, he says, the $430 million fine is an inexpensive "cost of doing business." (Related story: Whistle-blower started scrutiny)

In addition to the fine, Pfizer agreed to tighter rules to ensure compliance with drug-marketing laws. It will also contribute millions of dollars to states to educate doctors about Neurontin.

Approved for two conditions

Warner-Lambert's offense was marketing Neurontin to doctors for purposes other than as a supplemental anti-seizure medication for epileptics. That was the only use approved by the Food and Drug Administration during Neurontin's early years, when prosecutors say Warner-Lambert's illegal marketing took place.

In 2002, the FDA said Neurontin also could be used for nerve pain related to shingles.

Doctors can prescribe FDA-approved drugs for other purposes, so-called off-label uses. But federal law forbids pharmaceutical companies to market drugs for treatments not FDA-approved.

The Justice Department says that's what Warner-Lambert did from shortly after introducing Neurontin in 1994 until 2000. Prosecutors alleged that Warner-Lambert lied to doctors about the drug's effectiveness, paid doctors to allow a sales representative to sit in on sessions with patients and paid doctors, some up to $250,000, to unethically talk up Neurontin to other doctors.

In fact, the list of ailments that Warner-Lambert claimed Neurontin alleviated was so long covering pain, headaches, bipolar disorder, attention deficit disorder, alcohol detoxification that some Warner-Lambert employees dubbed it the "snake oil" list, government documents say.

The strategy worked. In 2002, 94% of Neurontin's sales were for off-label uses, up from40% in 1995, the government estimates, citing company documents and independent market research. Wall Street firm Lehman Bros. estimates that 90% of Neurontin sales are currently off-label.

Doctors consider the drug relatively safe with few side effects. But prosecutors said Warner-Lambert's actions caused Medicaid to pay for prescriptions it should not have. They also said patients could have been harmed by taking a drug not proved safe and effective for their condition.

"The aggressive marketing campaign by Warner-Lambert resulted in real increased costs to the states, insurers and consumers," Vermont Attorney General William Sorrell said the day of the settlement. He noted a 30-day supply of Neurontin at a common dose costs $205.

Angry at the company

Steve Borcherding, 42, is a former Neurontin user. The father of three runs a home-repair business in Portland, Ore. He has bipolar disorder, an illness often called manic depression. People who have the disorder often cycle from euphoria to deep depression. Borcherding has hit psychotic states. If not on medication, he says, he might do things such as try to drive through a brick wall because he believes he'll pass through.

In 2001, his psychiatrist suggested he try Neurontin. He knew it wasn't FDA-approved for his illness. That didn't worry him, because many drugs for his condition are not FDA-approved.

He says he didn't know that two studies published in 2000 including one sponsored partly by Warner-Lambert had shown Neurontin was no more effective than a placebo for his disorder.

He says he began taking Neurontin along with another drug he'd been taking before. His wife, Karla Wolf, says Neurontin didn't seem to make a difference for her husband at first. She recalls his mania then increased, and he was hospitalized for five days.

Borcherding was then taken off Neurontin.

He isn't suing anyone. Since the government's settlement, the New York-based law firm of Finkelstein & Partners has filed at least five lawsuits alleging Neurontin caused suicides or attempted suicides. Borcherding says there's no way to prove that Neurontin caused his downward spiral. He'd had similar spirals before taking Neurontin and had been hospitalized while on other drugs.

He considers drug researchers "heroes" and trusts the doctor who prescribed Neurontin for him.

But he's angry at the company's promotion of the drug for his illness. "They had the data that this was not an effective drug, and they ignored that data," he says. "I really have faith in the scientific process and Western medicine and empirical evidence, and they hijacked that process. They betrayed it."

Pfizer says that the company will vigorously defend itself against all lawsuits and that it knows of no individual harmed by Neurontin. It also says that many drugs are used off-label, including cancer drugs, and that the government did not allege illegal conduct after Pfizer bought Warner-Lambert in 2000.

As part of the settlement, Warner-Lambert pleaded guilty to conduct before Aug. 21, 1996, only, even though prosecutors alleged illegal actions occurred later, too. The settlement made it possible for the company to continue to participate in federal health care programs such as Medicaid, despite an Aug. 21, 1996, health care fraud law that might have led to its exclusion. Pfizer would not make an executive available to be interviewed for this story.

Used by millions

Almost 12 million people have used Neurontin since 1994, Pfizer says. Sixty countries allow it to treat pain. Even though the U.S. has approved it for only two conditions, Neurontin's popularity has snowballed. For the past three years, it has been the third-biggest drug cost for Oregon's Medicaid program. That occurred despite a lack of strong scientific support for its off-label uses.

In 2003, the Journal of Managed Care Pharmacy published a literature review of Neurontin studies. The author, Alicia Mack, a doctor of pharmacy, concluded Neurontin was not the "optimal" treatment for the majority of off-label uses except nerve pain related to diabetes and for frequent migraines.

One rigorous study published in 2002 dubbed it an expensive anti-migraine option: $138 per migraine prevented.

Assistant U.S. Attorney Thomas Kanwit in Boston, one of the chief prosecutors on the Neurontin case, says his biggest hope is that the case changes drug industry marketing practices.

As far as affecting Neurontin's momentum, Kanwit acknowledges the case may have little impact. Among the reasons:

Insurers have a hard time controlling drug prescriptions. Insurance companies and Medicaid programs can require doctors to get their approval before prescribing a specific drug. But it's rarely done with Neurontin, even though the allegations about fraudulent marketing became public in 2000.

Only four of 50 state Medicaid programs require preapproval of Neurontin prescriptions, USA TODAY found when it surveyed all of them after Pfizer's government settlement. Among major health insurers, only Aetna says it's considering preapproval.

Preapproval can hurt sales. Florida expects its July 1 decision to require preapproval for Neurontin will save more than $7 million in its $2.1 billion Medicaid drug program. Neurontin prescriptions in Maine's Medicaid program dropped 19% despite a 9% increase in eligible Medicaid clients after preapproval took hold in October. Massachusetts and Oregon also started requiring preapproval last year.

Other states and insurers are wary because restricting Neurontin's availability could hurt consumers who really need it. Preapproval rules are also costly and time consuming to administer. What's more, lower-cost generic competitors may become available in the USA as soon as next year. To require preapproval for Neurontin prescriptions now may cost more than it saves, says Robert Seidman, chief pharmacy officer for WellPoint Health Networks, parent of Blue Cross of California.

"We have to make sure the payoff is worth the hassle factor," agrees Nancy Nesser, pharmacy director of the Oklahoma Health Care Authority.

The authority decided it wasn't in 2002 after its own study suggested that fewer than 10% of its clients on Neurontin suffered from epilepsy or shingles, Neurontin's two FDA-approved uses. "You don't want to put a roadblock on an epilepsy drug," Nesser says.

Oklahoma's Neurontin costs surpassed $5 million in 2003, up from $4.2 million the year before.

Medicaid laws fuel off-label prescribing. To ensure that Medicaid patients had good access to drugs, Congress in the early 1990s decreed Medicaid should pay for a drug for a use that is FDA-approved or supported by citations in one of three medical directories.

One directory, Drugdex Information System, owned by Canada's Thomson Corp., says Neurontin is effective or possibly effective in treating 46 ailments. Often, that judgment is based on case studies of a small number of patients or studies in which patients knew they were taking the drug, which can skew results. The FDA requires more rigorous testing for approval.

The other directories cite Neurontin for FDA-approved conditions and six pain conditions.

Nicotine withdrawal is one condition Drugdex says Neurontin is "possibly effective" in treating. That is based on the 2001 case of a 54-year-old man who had also been alcohol-dependent and who was being treated for depression. While on a daily dosage of 2,400 milligrams a day, costing about $8 to $12 a day based on today's online prices, he abstained from nicotine for 10 weeks. The study's author suggested further study.

Medicaid could refuse to pay for Neurontin for nicotine withdrawal, says Barbara Dean, head of Texas' Medicaid drug program. But it "would be taking its chances," she says, because drug companies can argue that Medicaid laws stipulate it pay.

Drugdex editor Michael Soares says Drugdex hasn't changed its criteria for what it includes in decades. Drugdex became one of the three directories in 1997. "I realize there's implications for (Medicaid) reimbursements," he says.

But Drugdex's No. 1 goal is to inform pharmacists and doctors about a drug's use and how it works, he says. The nicotine study was published in a reputable medical journal, and Drugdex's review board, which includes doctors, included it because "people might be talking about it." Drugdex notes support for Neurontin for nicotine withdrawal is poorly documented.

Doctors want to help patients. They'll try drugs if they think they might work, even if the FDA hasn't sanctioned them for a particular treatment.

Jim Moorman, CEO of Taxpayers Against Fraud, spends his life working on ways to reduce fraud, thus taxes. He applauds the Justice Department's action against Pfizer.

Yet he also takes Neurontin because "it seems to work" in alleviating his restless-leg syndrome. Neurontin is not FDA-approved to treat RLS, in which legs inadvertently jerk. No drugs are, but there is some evidence that Neurontin can help RLS patients.

"Let's recognize this: There are off-label uses for Neurontin that are valid," Moorman says. "But (Warner's) marketing department didn't care if the uses were valid or not."

Thomas Turek, medical director of the Oregon Health Plan, also says a drug that may not work for many may work for an individual, even if it has only a placebo effect.

Should onus be on doctors?

Despite Pfizer's fraud settlement, psychiatrist Suzanne Vogel-Scibilia remains sold on Neurontin. She has 1,000 patients in her Pennsylvania practice. A board member for the National Alliance for the Mentally Ill, she says the bipolar studies on Neurontin are not exhaustive enough.

She prescribes Neurontin, always with another drug, to ease anxiety and sleep disorders in mild bipolar cases. As a bipolar patient, she takes it, too. "As a doctor, I want the freedom to prescribe what I think works," she says.

She says doctors should check the validity of drug studies and decide prescriptions case by case.

But Jerome Avorn, author of an upcoming book, Powerful Medicines, says time-pressed doctors turn most often to drug representatives for drug information. Avorn, a doctor with Harvard Medical School and Brigham and Women's Hospital, also says doctors too often attempt to learn whether a drug works for a patient by trying it. "We ought to have a better system than that." He advocates more studies and easier access to data.

Even Oregon, with new preapproval rules, will continue to pay for Neurontin for existing bipolar users. "It doesn't fit with the science ... but people aren't machines, so we have to use some of the art (of medicine) as well as the science," Turek says.

Janet Marquez, 25, doesn't pay much mind to studies. She looks at her life. Several years ago, Marquez spent four months in a psychiatric hospital. Diagnosed as bipolar, she tried other drugs. They didn't work, she says. About four years ago, she started Neurontin. She's now in college, living on her own and volunteering at a local library.

When Oregon last year threatened not to pay for her Neurontin, her doctor wrote a letter for her.

Oregon still pays for Marquez's Neurontin. "If it doesn't work, then why do I feel better?" she says.

False Marketing Nets Pfizer A $430M Fine

Wed, 19 May 2004 00:00:00 -0700

In a settlement worked out between Pfizer and the United States Justice Department, the pharmaceutical company agreed to plead guilty to charges it illegally promoted non-approved uses for its anti-epilepsy drug Neurontin and pay $430 million in fines.

The government alleged that Warner-Lambert Corp., purchased by Pfizer in 2000, flew doctors to resorts and paid them huge fees to tout and prescribe the drug as a pain reliever, a cure for bipolar disorder, other psychiatric disorders and Lou Gherigs Disease when there was no indication the medicine had any effect at all on any of those maladies.

Neurontins sales had climbed from $97.5 million in 1995, when the false advertising began, to nearly $2.7 billion by 2003.

The settlement includes a $240 million criminal fine, the second-largest criminal fine imposed in a health-care fraud prosecution, according to the Justice Department. This illegal and fraudulent promotion scheme corrupted the information process relied upon by doctors in their medical decision-making, thereby putting patients at risk, Michael Sullivan, U.S. Attorney in Boston, Mass., said in a prepared statement.

David Franklin, the whistleblower in the case and a scientist in the Boston-based Parke-Davis division of Warner Lambert, reported the marketing abuses to authorities. He will receive $24.6 million as part of the settlement.

Franklin told the Associated Press what Pfizer did was standard operating procedure in the pharmaceutical business.

Under an agreement with prosecutors, Pfizer agreed to plead guilty to two counts of violating the Food, Drug and Cosmetic Act and pay a $240 million criminal fine.

Pfizer will also pay $152 million in civil damages for losses incurred by the Medicaid program and $38 million as part of a settlement with 50 state attorneys general.

New Jersey will receive $1.8 million, with $1.55 million going to its Medicaid program and the remainder to the Division of Consumer Affairs.

Pfizer spokesman Paul Fitzhenry blamed the violations on the Warner Lambert pre-buyout and said the advertising began eight years ago, well before Pfizer bought the company.

He added those practices are banned by the companys current ethics policy.

Pfizer is committed to compliance with all health-care laws and FDA requirements and to high ethical standards in all aspects of its business practices, the company said in a statement.

The case began in 1996, when Franklin filed a lawsuit against drug maker Parke-Davis, saying it used an illegal marketing plan to drive up Neurontin sales.

Franklins lawsuit alleged the companys publicity plan included paying doctors to sign off on ghostwritten articles about Neurontin and to prescribe the drug for various uses. The company offered the doctors trips to Florida, the 1996 Atlanta Olympics and Hawaii.

According to the Justice Department, one doctor received close to $308,000 to speak at conferences about the drug.

Neurontin was shown to be less effective than a placebo for treating bipolar disorder, but the company did not publish those findings and instead told doctors the drug was highly effective for treating the disorder, according to the lawsuit.

Franklin filed his lawsuit under the U.S. False Claims Act, which allows private citizens to sue on behalf of the government and receive a portion of awards in cases where companies are defrauding the government.

The settlement was the second- largest of its kind since TAP Pharmaceutical paid an $875 in 1999.

Pfizer Guilty, To Pay $430M

Fri, 14 May 2004 00:00:00 -0700

Pfizer Inc. will plead guilty to criminal charges and pay $430 million in fines to settle charges that a company it bought illegally promoted non-approved uses for a drug.

The settlement with the world's largest pharmaceutical company over Warner-Lambert, which Pfizer bought in 2000, includes a $240 million criminal fine the second-largest ever imposed in a health-care fraud prosecution, the Justice Department said. Pfizer also will pay $152 million in civil fines to be shared among state and federal Medicaid agencies. Another $38 million would go to state consumer-protection agencies.

Under the agreement announced Thursday by federal prosecutors, the company acknowledged spending hundreds of thousands of dollars to promote non-approved uses for the anti-seizure drug Neurontin. The company said the activity occurred years before it bought Warner-Lambert.

The case began in 1996, when scientist David Franklin filed a whistleblower lawsuit under the U.S. False Claims Act, which allows private citizens to sue on behalf of the government and receive a portion of awards in cases where companies are defrauding the government. Franklin will receive $26.6 million as part of the settlement.

Franklin's suit alleged that, to drive up sales in the 1990s, drug maker Parke-Davis and its parent company Warner-Lambert promoted the drug Neurontin for relieving pain, headaches, bipolar disorder and other psychiatric illnesses though it was approved only as an epilepsy drug. While doctors can prescribe drugs for any use, promoting drugs for so-called "off-label uses" is prohibited by the Food and Drug Cosmetic Act.

The lawsuit alleged the company's plan included paying doctors to put their names on ghostwritten articles about Neurontin and to induce them to prescribe the drug for various uses by giving them tickets to sporting events, trips to golf resorts and speakers fees.

Pfizer Will Pay Millions To Settle

Fri, 14 May 2004 00:00:00 -0700

Pfizer, the world's largest pharmaceutical company, pleaded guilty Thursday and agreed to pay $430 million to resolve criminal and civil charges that it paid doctors to prescribe its epilepsy drug, Neurontin, to patients with ailments that the drug was not federally approved to treat.

Oregon, one of the states to participate actively in the investigation, will receive $2 million from the settlement and will be the host state for two funds that aim to make more information on pharmaceuticals available to the public.

A former company adviser who brought a lawsuit under a federal "whistle-blower" law will receive $26.64 million from the settlement.

Pfizer will plead guilty to violating the Food, Drug and Cosmetic Act. Besides a $240 million criminal fine, the company will pay $152 million in civil fines to be shared among state and federal Medicaid agencies, of which Oregon will receive $1.3 million. Another $38 million would go to state consumer-protection agencies, including $700,000 to Oregon's.

The agreement calls for housing two education accounts worth $28 million in Oregon. A $21 million account will award grants to government agencies, academic institutions and nonprofits. The grantees will be asked to create programs with unbiased research and information to educate consumers and doctors about pharmaceutical products. A committee of eight attorneys general, including Oregon's, will choose the grant recipients.

Another $6 million account will go toward a national advertising campaign to give consumers and doctors fair and balanced information about Neurontin and other prescription drugs. A group of six attorneys general, including Oregon's, will select the advertising firms involved. As much as $1 million of the $28 million in the accounts will be used later to evaluate the effectiveness of the grant programs.

Because the funds sit in Oregon and because state Attorney General Hardy Myers will be on both selection committees, organizations and advertisers in Oregon are "well-suited" to receive account funds, to be doled out during the next six years, said Kevin Neely, a spokesman for the attorney general's office.

Formulating the process and criteria for how the fund recipients will be chosen may begin as soon as today, Neely said.

Pfizer encouraged doctors to prescribe Neurontin for patients with bipolar disorder, a psychological condition, even though a study had shown that the medicine was no better than a placebo in treating the disorder. Other disorders for which the company illegally promoted Neurontin included Lou Gehrig's disease, attention deficit disorder, restless leg syndrome and drug and alcohol withdrawal seizures.

Although doctors are free to prescribe any federally approved drug for whatever use they choose, pharmaceutical companies are not allowed to promote drugs for nonapproved purposes.

Neurontin was initially approved to treat epileptic seizures in patients who had failed to improve using other treatments, but it has become one of the biggest-selling drugs in the world, with sales last year of $2.7 billion. Nearly 90 percent of the drug's sales continue to be for ailments for which the drug is not an approved treatment, according to recent surveys.

Warner-Lambert program

"This illegal and fraudulent promotion scheme corrupted the information process relied upon by doctors in their medical decision-making, thereby putting patients at risk," said the U.S. attorney in Boston, Michael Sullivan, in a statement Thursday. Pfizer, in a statement Thursday, said the illegal marketing had been conducted by Warner-Lambert before Pfizer acquired that company in 2000.

"Pfizer has cooperated fully with the government to resolve this matter, which did not involve Pfizer practices or employees," the company said.

Pfizer took a $427 million charge in January against its fourth-quarter 2003 earnings to pay for the expected settlement. The government calculated that the company's illegal promotions brought it $150 million in ill-gotten gains. A standard multiplier was used to come up with the $430 million fine.

The case is one of many undertaken in recent years by federal prosecutors in Boston and Philadelphia who are examining efforts by drug companies to market their drugs for unapproved uses and pay off doctors for prescriptions. And although the pharmaceutical industry recently adopted voluntary guidelines that have eliminated many of the gifts and payments once routinely dispensed to doctors, the industry's aggressive promotions continue.

Although the agreement announced Thursday clears Pfizer of any further liability in the Neurontin matter, the government may still criminally charge former Warner-Lambert executives who concocted and approved the plans, according to the settlement. Documents in the case show that Warner-Lambert's illegal marketing activities were approved by some of the company's top executives.

The case originated in 1996 when Dr. David P. Franklin quit his job as a medical adviser to Warner-Lambert's sales staff, after realizing that he was being asked to promote Neurontin well beyond the condition for which federal drug regulators had approved it. Franklin filed a lawsuit under a Civil War-era whistle-blower statute that allows private individuals to sue on behalf of the government, with the prospect of sharing in any financial awards.

His lawyer, Thomas Greene, said Thursday, "I hope this encourages other employees of companies that see corporate wrongdoing to come forward and expose it."

Says practice widespread

In an interview, Franklin said he often sat in doctors' waiting rooms with medical liaisons from other drug companies who were there to do exactly what he was doing -- promote unapproved uses of medicines. "What we did was standard practice in the pharmaceutical industry," Franklin said.

Although Franklin has been out of the pharmaceutical industry for eight years he is now a marketing executive with the medical device maker Boston Scientific -- he scoffed at the notion that things have changed much in drug marketing.

"Ninety percent of Neurontin's sales are for patients for which there is no proof that the drug works," he said. "There's been an explosion of off-label drug use in the years since I left."

Pfizer Set To Cough Up $430M

Fri, 14 May 2004 00:00:00 -0700

David Franklin says it was worries about patients who may have been harmed that sustained him in an 8-year-fight against a giant drug maker that ended yesterday with a $430 million settlement.

Franklin, who spent four months as a liaison to doctors for Parke-Davis Inc. now owned by Pfizer, charged the company illegally promoted off-label uses for Neurontin, an epilepsy drug.

As a whistleblower, Franklin, 42, will get $26.6 million from the settlement.

Government prosecutors eventually took up the charge and yesterday announced the settlement, which includes a $240 criminal fine.

Massachusetts will get $8.3 million through the settlement.

According to Franklin, the company urged its representatives to give misleading and wrong information to doctors to encourage them to prescribe Neurontin for ailments it hadn't been approved to treat.

Pfizer officials said yesterday that the settlement pertains to practices of Parke-Davis before Pfizer bought its owner, Warner Lambert.

Doctors are allowed to prescribe drugs for uses that haven't been approved by the U.S. Food and Drug Administration. But companies can't promote those uses.

Franklin said he should have realized during his interview for the job that there was a problem. He was asked questions about how he would handle certain ethical situations that, in retrospect, were unusual, he said.

But he wanted to use his Ph.D. in microbiology in the pharmaceutical industry. He said he liked the idea of working with doctors to give them information to help their patients.

Franklin said the company told him to tell doctors that studies showed the drug could be used to treat such things as bi-polar disorders. In reality, the company had a study showing a placebo had outperformed Neurontin in treating bi-polar conditions.

Franklin said he figured out something was wrong when a doctor confronted him.

``I realized the company was deceiving me,'' Franklin said. ``I learned that I was paid to mislead physicians and put patients at risk. It was a situation I couldn't live with.''

Franklin, who now works for Boston Scientific, said there were times when he wanted to walk away from it all.

``All it took (to hang on) was the recognition that to this day patients are being injured by this kind of practice,'' he said.

Pfizer to Pay $420 Million in Illegal Marketing Case

Fri, 14 May 2004 00:00:00 -0700

Pfizer, the world's largest pharmaceutical company, pleaded guilty yesterday and agreed to pay $430 million to resolve criminal and civil charges that it paid doctors to prescribe its epilepsy drug, Neurontin, to patients with ailments that the drug was not federally approved to treat.

Of that settlement, $26.64 million will go to a former company adviser who brought a lawsuit under a federal "whistleblower" law.

The company encouraged doctors to use Neurontin in patients with bipolar disorder, a psychological condition, even though a study had shown that the medicine was no better than a placebo in treating the disorder. Other disorders for which the company illegally promoted Neurontin included Lou Gehrig's disease, attention deficit disorder, restless leg syndrome and drug and alcohol withdrawal seizures.

Although doctors are free to prescribe any federally approved drug for whatever use they choose, pharmaceutical companies are not allowed to promote drugs for nonapproved purposes. Neurontin was initially approved to treat epileptic seizures in patients who had failed to improve using other treatments, but it has become one of the biggest-selling drugs in the world, with sales last year of $2.7 billion. Nearly 90 percent of the drug's sales continue to be for ailments for which the drug is not an approved treatment, according to recent surveys.

"This illegal and fraudulent promotion scheme corrupted the information process relied upon by doctors in their medical decision-making, thereby putting patients at risk," said the United States attorney in Boston, Michael Sullivan, in a statement yesterday.

Pfizer, in a statement yesterday, said that the illegal marketing had been conducted by Warner-Lambert before Pfizer acquired that company in 2000.

"Pfizer has cooperated fully with the government to resolve this matter, which did not involve Pfizer practices or employees," the company said.

Pfizer took a $427 million charge in January against its fourth-quarter 2003 earnings to pay for the expected settlement. The government calculated that the company's illegal promotions brought it $150 million in ill-gotten gains. A standard multiplier was used to come up with the $430 million fine.

The case is one of many undertaken in recent years by federal prosecutors in Boston and Philadelphia who are examining efforts by drug companies to market their drugs for unapproved uses and pay doctors for prescriptions. And while the pharmaceutical industry recently adopted voluntary guidelines that have eliminated many of the gifts and payments once routinely dispensed to doctors, the industry's aggressive promotions continue.

Companies continue to underwrite physician education seminars where unapproved uses of their drugs are discussed. They continue to hire advertising agencies to conduct clinical trials and ghostwriters to write up the studies for experts listed as authors. And they often hire physicians as consultants, arrangements that call into question a physician's independence in deciding what drugs to prescribe for patients.

Other companies that have been fined for drug marketing abuses include TAP Pharmaceuticals, which in 2001 paid $875 million the largest such fine so far. Last year, Bayer paid $257 million. Schering-Plough is currently under investigation for its sales practices.

While the agreement announced yesterday clears Pfizer of any further liability in the Neurontin matter, the government may still criminally charge former Warner-Lambert executives who concocted and approved the plans, according to the settlement. Documents in the case show that Warner-Lambert's illegal marketing activities were approved by some of the company's top executives.

The case had its origins in 1996 when Dr. David P. Franklin quit his job as a medical adviser to Warner-Lambert's sales staff, after realizing that he was being asked to promote Neurontin well beyond the condition for which federal drug regulators had approved it. Dr. Franklin filed a lawsuit under a Civil War-era whistleblower statute that allows private individuals to sue on behalf of the government, with the prospect of sharing in any financial awards.

In an interview, Dr. Franklin said that he often sat in doctors' waiting rooms with medical liaisons from other drug companies who were there to do exactly what he was doing - promote unapproved uses of medicines. "What we did was standard practice in the pharmaceutical industry," Dr. Franklin said.

And although he has been out of the pharmaceutical industry for eight years he is now a marketing executive with the medical device maker Boston Scientific he scoffed at the notion that things have changed much in drug marketing. "Ninety percent of Neurontin's sales are for patients for which there is no proof that the drug works," he said. "There's been an explosion of off-label drug use in the years since I left."

It is only after careful examinations of the results of expensive clinical trials that federal drug regulators approve treatments for specific medical conditions. While doctors can freely prescribe approved drugs for any treatment, drug companies must carefully restrict their communications about these so-called off-label uses, limiting themselves to handing out scientific articles, for example, or hiring experts to give lectures to physicians about the unapproved uses.

Warner-Lambert went beyond those strictures by flying doctors to Hawaii, the 1996 Olympics in Atlanta and Florida, paying them consulting fees and providing expensive dinners at which unapproved uses of Neurontin were discussed. The company also paid some doctors to allow sales representatives to sit with them as they saw patients.

The patient visits were the last straw for Dr. Franklin, he said. He recalled that the company distributed a voice mail message from a sales representative who described the day he had spent with a physician and his patients. "The sales representative said he explained to the physician with the patient right there on the table why Neurontin was the best possible medicine," Dr. Franklin said. "That's practicing medicine without a license."

These marketing practices, though, were extremely effective, according to internal company documents. Doctors who attended dinners given by the company to discuss unapproved uses of Neurontin wrote 70 percent more prescriptions for the drug than those who did not attend, one memorandum showed.

Generic versions of the drug could be introduced later this year. Pfizer is hoping to gain approval soon for a successor medicine called Lyrica, or pregabalin, as a treatment for epilepsy and neuropathic pain. Internal company documents show that Warner-Lambert executives decided against seeking approval from federal drug regulators for other uses of Neurontin for fear that generic versions would one day undercut sales of Lyrica.

Part of the government's rationale for bringing the case was that Warner-Lambert's marketing schemes led physicians to prescribe to Medicaid patients who should not have received the drug, costing federal and state governments millions of dollars. Of the $430 million fine, $106 million will go to the 50 states, which share with the federal government the costs of the Medicaid program.

Pfizer Sets Aside $403M For Possible Settlement

Fri, 23 Jan 2004 00:00:00 -0800

Pfizer Inc. indicated it is closer to settling allegations of drug fraud charges, saying it has set aside $403 million for federal and state prosecutors over its promotion of what has become the country's top-selling epilepsy drug, Neurontin.

As part of its 2003 financial results filed with federal regulators yesterday, Pfizer said it took a charge of $403 million in the fourth quarter, an amount the company believes "will be sufficient to resolve all outstanding federal and state governmental investigations related to Neurontin" as well as a civil whistle-blower lawsuit brought by a former Massachusetts employee.

If Pfizer settles the criminal and civil cases for close to that amount, it would be one of the largest settlements for drug fraud in US history. In June, drug maker AstraZeneca Pharmaceuticals agreed to pay $355 million to resolve criminal and civil allegations that the company inflated the price of its prostate cancer drug and bribed doctors to prescribe it. At the time, that settlement was second in size only to the $885 million TAP Pharmaceutical Products Inc. paid in 2001 to settle similar allegations in a Boston case.

Federal and state prosecutors, angry over the soaring costs of prescription drugs to the state and federal Medicaid program, use these settlements to recoup money spent by the government. In the Neurontin investigation, federal and state prosecutors have accused the company of illegally promoting the drug to doctors through a variety of methods including kickbacks.

The US attorney's office in Boston, which has been investigating Warner-Lambert's promotion of Neurontin, declined to comment on settlement talks yesterday. Pfizer bought Warner-Lambert in 2000 and with it any liability from Warner-Lambert's sales practices.

Last May, federal prosecutors made a filing in the whistle-blower case in US District Court in Boston that for the first time outlined their belief that Warner-Lambert engaged in an illegal marketing scheme to increase sales of its epilepsy drug.

Pfizer also declined to comment yesterday except to say that "discussions have recently advanced to a point where it is appropriate" to report an amount required to resolve the investigations. Pfizer spokesman Paul Fitzhenry declined to comment on whether the US attorney plans to file criminal charges against the company.

Former Warner-Lambert employee David Franklin and his attorney Thomas Greene filed the whistle-blower lawsuit more than six years ago, saying the company gave doctors illegal financial incentives to prescribe Neurontin and illegally promoted the drug for uses that were not approved by federal regulators.

Based largely on voice-mail messages and documents collected by Franklin, the US attorney's office said in its court filing that the company gave doctors kickbacks in the form of lavish trips and tickets disguised as educational or consulting payments. In one instance, prosecutors said, the company paid for doctors to stay five days in Atlanta during the 1996 Summer Olympics. The company covered the doctors' meals, use of a resort, and motorcoach travel to the games. Agendas for the meeting listed 10.5 hours of business meetings, including one session devoted to off-label uses for Neurontin, prosecutors said.

Prosecutors also said Warner-Lambert and its subsidiaries misled doctors into believing that programs discussing uses for Neurontin were independent educational programs when they actually were marketing efforts led by the company. Pfizer executives have repeatedly refused to comment on the charges, only saying the allegations concern company activities during the mid-1990s, years before Pfizer purchased Warner-Lambert.

Meanwhile, sales of Neurontin have soared. The company reported worldwide sales of Neurontin in 2003 grew 19 percent to $2.7 billion.

Pfizer said fourth-quarter net income fell to $602 million, or 8 cents a share, from $2.86 billion, or 46 cents, a year earlier. Excluding acquisition costs and legal expenses, profit was 53 cents a share, beating the average analyst estimate of 51 cents in a Thomson Financial survey. Sales jumped 52 percent, boosted by the takeover of Pharmacia Corp.

Fourth-quarter revenue at Pfizer climbed to $14.2 billion from $9.3 billion, helped by sales of Celebrex, Bextra, and Lipitor, a cholesterol-lowering drug Pfizer acquired with its purchase of Warner-Lambert.

Whistleblower's Lawsuit Being Closely Watched By Drug Industry

Sun, 10 Aug 2003 00:00:00 -0700

When Dr. Edgar L. Ross wants information about anti-pain drugs, he does need to look far: He can attend dinner meetings funded by drug companies, fly to industry-sponsored conferences and seek out company representatives eager to answer questions.

But none of that, he said, influences his decisions about prescriptions. Only one source does: "peer-reviewed journals I read and trust."

Ross, medical director of the Pain Management Center at Boston's Brigham and Women's Hospital, said he began prescribing the anti-seizure medication Neurontin after he read about it in a medical journal in the mid-1990s, convincing him the drug worked for pain. He said he doesn't remember whether he knew then that an author of the paper was paid thousands of dollars by Neurontin's manufacturer in what a federal whistleblower now alleges was part of an elaborate scheme to skirt federal rules for promoting drugs.

The lawsuit in U.S. District Court in Boston charges that Neurontin's manufacturer, Parke-Davis, and parent company, Warner Lambert, which merged with Pfizer Inc. two years ago, flouted federal law in the 1990s with an illegal marketing plan intended to drive up Neurontin's sales.

David Franklin's lawsuit is being closely watched by the drug industry and its critics, who say pharmaceutical companies use subtle tactics to increase sales of drugs for other uses than the Food and Drug Administration has not yet approved a practice known as "off-label" uses.

The federal government, 11 states and the District of Columbia have joined Franklin's complaint, which has provided a rare look at the tactics drugmakers use to provide information about different uses of new drugs to doctors.

Franklin, who worked as a Parke-Davis drug liaison for less than five months in 1996, claims the company adopted a strategy to increase publicity about Neurontin's effectiveness for unapproved uses such as relieving pain, headaches and psychiatric illnesses defrauding the government in the process by encouraging doctors to write prescriptions and seek Medicaid reimbursement.

The strategy allegedly included paying doctors to put their names on ghostwritten articles and, in one case, publish a book on Neurontin for $300,000 and fly them to lavish "educational" junkets. The company wanted "Neurontin champions" at prestigious teaching hospitals to spread the word about the drug and take part in phony studies, the suit said.

Franklin alleges that he and other liaisons were instructed to lie about Neurontin's effectiveness, and that a Parke-Davis medical director told him that what the company was doing was "brazenly criminal."

Franklin, who now works for the medical device maker Boston Scientific, stands to claim a portion of any settlement if the lawsuit is successful. His attorney, Thomas M. Green, refused repeated requests for interviews with Franklin.

Today, about 80 percent of Neurontin prescriptions are for off-label uses. The FDA has since approved the drug's use for one type of pain.

Pfizer has strongly disputed Franklin's claims in court documents, saying "no evidence supports the allegations that false statements were made."

"As a result, the allegations provided by (Franklin) that the statements are false are unsupported, conclusory assertions made by (Franklin), with no evidentiary support," Pfizer attorney David B. Chaffin wrote.

A spokeswoman for U.S. Attorney Michael Sullivan, whose office has joined Franklin in the lawsuit, declined to comment on the Neurontin case.

Ahaviah Glaser, director of the Prescription Access Litigation Project in Boston, which has brought a similar lawsuit against Pfizer and Parke-Davis in California, said doctors often rely on biased drug marketing information disguised as education.

"I think everyone's feet need to be held to the fire," she said. "I do think that a few strong court opinions critiquing these practices will be very helpful in discouraging these practices from being as widely used as they are."

Once the FDA has approved a drug, the agency allows doctors to prescribe it for other uses. But with few exceptions, it forbids companies and their representatives from promoting such off-label uses.

The FDA has purposefully left its definition of "promotion" vague, according to former FDA associate commissioner Marc J. Scheineson.

"The courts have consistently said in the United States that they want consumers and they want physicians to get as much information as they can, as long as that information isn't false or misleading," he said. "Keeping it ambiguous enough to create a penumbra around most marketing pieces, you're never sure whether this will trigger FDA enforcement action."

In the lawsuit, Franklin cites Ross as an example of how the scheme increased Neurontin sales, saying the doctor began writing prescriptions and asking for reimbursement from Medicaid right after he attended a conference in Atlanta on pain medications in 1997. Ross said the reason Medicaid has no records of his Neurontin prescriptions in Massachusetts before that conference was because he only recently moved to the state. But when asked what has influenced his prescription writing, Ross cited the 1995 article by Dr. Gary Mellick and his brother, Dr. Larry Mellick, saying it first drew his attention to Neurontin's efficacy for pain.

Franklin's lawsuit cites Gary Mellick's writing as part of the scheme, saying he was paid at least $21,000 by Parke-Davis and didn't divulge the income in his published articles.

Ross said he cannot remember whether he knew that Parke-Davis paid Mellick, but he said he wants to know whether doctors are being paid to write about drugs. "I definitely rely on accurate information, and I look at the bottom of the article for who's funding it," he said.

Numerous calls placed to Gary Mellick's office in Ohio were met with busy signals, and a message left at a residence for a Gary Mellick in Grafton, Ohio, was not returned.

Drug Giant Accused of False Claims

Fri, 11 Jul 2003 00:00:00 -0700

The questions began with the confession of an insider at one of the nations largest pharmaceutical firms. He says his former company deliberately distorted information about one of its drugs, possibly putting lives at risk, and costing patients and taxpayers millions of dollars. Dateline went looking for some answers and has the results of a year-long investigation into what may be one of the biggest medical deceptions in history. NBCs John Hockenberry reports.

DAVID FRANKLIN: I was trained to deceive, to lie to doctors.

John Hockenberry: So these doctors were completely misled?

Franklin: Absolutely.

Who would train and then pay someone to mislead doctors? Scientist David Franklin says pharmaceutical company Warner-Lambert paid him to do that back in 1996.

Franklin: It was my responsibility to leverage the trust that physicians had with pharmaceutical companies to corrupt the relationship between the physician and the patient.

John Hockenberry: Your job was to find trust, and exploit it, to produce more sales for Warner-Lambert.

Franklin: Absolutely.

Since he was a little boy growing up in Rhode Island, Franklin says, he wanted to be a scientist. But he wanted to use that science to help people, doing medical research to cure disease. So Franklin got his Ph.D. in biology at the University of Rhode Island and from there became a researcher at the prestigious Dana Farber Cancer Institute. After more than three years as a researcher, Franklin wanted to get out of the lab. He found a job at Parke-Davis, a division of Warner-Lambert. He would be a medical liaison, using his scientific expertise to explain the scientific merits of drugs to doctors.

Franklin: The medical liaison was supposed to be fair and balanced, where the physician could trust what the medical liaison was telling them.

Hockenberry: So, doctors wouldnt necessarily see you as a company guy, as much as they would see you as a scientist. As as a medical doctor, like them in a way.

Franklin: Exactly. A person whose primary responsibility is to care of the patients, making sure that the doctor, to enable the doctor to practice the best possible medicine that science would allow at this point in time.

Hockenberry: So, a doctor needs more drugs for their practice. They call the salesman. But if they have questions about the medical use of that drug, they call you.

Franklin: Exactly.

But almost immediately, Franklin says, he became little more than a salesman. The job he thought would be about caring for people turned out to be little more than caring for the companys bottom line. With his Ph.D. and the title of doctor, Franklin says he became part of a broad mission to deceive, even entice doctors to prescribe drugs to patients whether it was scientifically justified or not.

Franklin: It was a matter of leveraging, corrupting, if you would, perverting the science, to greatly increase sales and profitability.

This corporate whistleblower, telling his story to Dateline in his first broadcast interview, has rocked the pharmaceutical industry to its core. Pieced together with confidential documents and taped voicemails, youll see a portrait of sales over science.

But mostly this is the story of how David Franklin helped one little drug become a star: Gabapentin, one of the drugs Franklin was responsible for, which goes by the brand name Neurontin. Neurontin is a useful and generally safe drug. The Food and Drug Administration approved it in 1993, but for only one use to help control epileptic seizures and only if taken in conjunction with another drug.

But Franklin says he soon learned that Warner-Lambert had plans for Neurontin, the little epilepsy drug, a plan to go directly to doctors and get them to prescribe Neurontin for all kinds of uses the FDA hadnt approved, called off-label uses.

Hockenberry: Warner-Lambert basically told you, The FDA says, scientifically, Neurontin treats epilepsy. But we can convince doctors. And heres how youll do it, to use Neurontin for a dozen other things.

Franklin: Absolutely. This was holding their hands and pushing them into to using Neurontin off-label.

And according to Franklin, the list of off-label uses was long, everything from attention deficit disorder to alcohol and drug withdrawal.

Now, off-label uses are nothing new. Doctors have been observing surprising new uses for drugs throughout history. Some of their discoveries become medical breakthroughs. One of the best-known examples is aspirin, once thought only good for pain, was found by doctors to increase blood circulation and prevent heart attacks.

Hockenberry: So its legal for doctors to say, You know what? I think this drug that is approved for your ear might be good for your throat.

Franklin: Not only is it legal, but its good medical practice.

But what is not legal is for a drug company to promote such unapproved, off-label uses or to exaggerate or report unproven breakthroughs to doctors as a way to get them to prescribe their drugs. Assistant U.S. Attorney Jim Sheehan, one of the countrys leading prosecutors of health care fraud, says such regulation exists because off-label use can be unsafe.

Sheehan: Every prescription drug is an inherently dangerous product with the potential to kill people as well as cure them. Thats why we have very strict regulation, thats why we have rules about what marketing and promotion they can do. Thats why we have rules about what they can produce and how they produce it.

Franklin says the rules went out the window from the moment he arrived on the job. For instance, he was told not simply to wait for doctors to ask him for his scientific opinions, but to instead target doctors and convince them to prescribe Neurontin, even though he knew that there was no FDA approval for its off-label uses.

Franklin says he was actually cold calling doctors, showing up like a salesman unannounced, and he found one thing about him opened a lot of doors.

Franklin: If I were to show up at a doctors office and say, Dr. Franklin is here to speak to Dr. Smith, Dr. Smith is much more likely to respond, as opposed to his receptionist calling him in his office, and saying, The Warner-Lambert sales rep is here to talk to you.

Franklin didnt say that he wasnt a medical doctor. Simply having the title of doctor, the Ph.D. he was so proud of, was all that mattered, Franklin says, and Dr. Franklin, it turns out, wore lots of hats, depending on whom he was visiting.

Hockenberry: So, you could have had a Ph.D. in economics or metallurgy, and it would have been just as fine?

Franklin: As long as it granted me the title of Dr. Franklin.

Hockenberry: What were you told to tell doctors about your background?

Franklin: We actually trained the sales representatives to introduce me as an expert in cardiovascular medicine.

Hockenberry: Were you?

Franklin: Absolutely not. My Ph.D. was in microbiology. At 9 in the morning I was an expert in cardiovascular medicine. At 10 when we walked across the street to a neurologist office, I was an expert in neurology.

And once inside, Franklin would make his pitch to the doctor. As I played the doctors part he showed me what he would say about Neurontin.

Franklin: Were really being inundated with information from across the country with physicians that are seeing a profound improvement in patients with bipolar disease so we would suggest that you titrate the patient up to 4,800 milligrams you will see marked improvement in their symptoms.

Hockenberry: So your suggestion to me is triple the dose and I might see some positive results.

Franklin: Absolutely. Its not a matter of might. You will see an improvement.

Hes a scientist who couldnt sound more certain. But is there any scientific validity to what he is saying about, for instance, bipolar disorder?

Franklin: None at all. And in fact, much of it is a fabrication. It is simply untrue.

Hockenberry: Was there any data that really supported the claims you were making?

Franklin: Not at all.

At best the claims were based on promising anecdotal and untested preliminary information that Franklin says was, promoted to doctors vigorously, directly and illegally.

Franklin: Not only is it illegal, its downright immoral. It doesnt just hurt the medical community, it has the potential of hurting patients.

But as youll see, there was nothing potential about the money to be made through these tactics. The billions to come were real as real as the patients whose stories are just beginning to emerge. Was their health compromised in a scientifically invalid campaign to raise sales of Neurontin?

A PATIENTS PERSPECTIVE

By the late spring of 1996, Franklin understood fully what he was doing in supplying misleading information to doctors about the drug Neurontin. What he didnt know, he says, was the effect on real patients. Its a knot in his stomach thats still there today.

Franklin: There hasnt been a day in six years that I havent thought about this and wrestled with my involvement in it.

Long after David Franklin began to have his first reservations about his job, 54-year-old Regina Adams got her own education about off-label uses of Neurontin.

Adams: My whole life was turned upside down, and I almost lost my life because of it.

Adams has bipolar disorder.

Hockenberry: When were you first diagnosed with a condition that might require ongoing use of pharmaceutical drugs?

Adams: About 11 years ago.

Hockenberry: And the symptoms you were exhibiting were?

Adams: Mania, mostly mania. Because I had just lost touch with reality.

Bipolar disorder occurs when the brain constantly cycles between mania and depression. Those who suffer from it can experience uncontrollable highs and lows.

Before she found a reliable treatment the disease played havoc with Adams life. She divorced and was in and out of hospitals. Doctors finally found a therapy that seemed to work, a drug called Depakote, FDA-approved for bipolar disorder.

Adams: That worked really well, worked for my head. But the side effect was weight gain.

Hockenberry: Weight gain?

Adams: I gained 100 pounds.

Adams wanted the benefits of Depakote without all the weight, so she asked her doctor for a different drug. The doctor recommended Neurontin At first Adams felt better and lost weight, but soon after things started to come apart.

Adams: I became more and more out of control. My whole personally, Im very a sweet, nice person. And I got hostile.

Hockenberry: Had you ever behaved like this before?

Adams: No. No. My ex-boyfriend said he had never seen me, when I was manic, act like this.

Adams went back to her doctor for help.

Adams: She just kept increasing the Neurontin. I didnt want to go any higher. I didnt want to get harmed from it.

Hockenberry: And your doctors response was, Increase the dosage.

Adams: Mm-hm.

Was there a risk? Adams dosage was tripled. Neurontin is known to have few if any side effects, one of its big selling points. But Neurontin was now Adams only treatment for bipolar disorder, which was very risky because Neurontin, it turns out, does essentially nothing for bipolar disorder and thats a scientific fact.

Dr. Gary Sachs: Neurontins a drug that has been studied under double-blind conditions twice. And in neither case did it prove to have any efficacy at all.

Hockenberry: In neither case?

Sachs: In neither case.

Dr. Gary Sachs runs the Bipolar Treatment Center at Massachusetts General Hospital.

Hockenberry: So, based on the science, someone with bipolar whos only taking Neurontin is essentially untreated.

Sachs: I think thats a fair assumption.

And for a bipolar patient like Adams, being untreated can be life-threatening. On Neurontin, Adams manic behavior became uncontrollable. She says she tried to kill herself. She ended up in the hospital.

Hockenberry: If your doctor gives you something, your assumption is that it works, and that somebodys shown that it works, right?

Adams: Right.

Hockenberry: In the case of Neurontin, was any of that true?

Adams: Not for me.

We tried to talk to Adams doctor at Meridian Behavioral Healthcare in Gainesville, Fla. and Adams said she had no problem allowing us see her medical records. But the company refused our request, issuing only a statement from her doctor acknowledging that Adams was treated with Neurontin but that the drug was discontinued when she experienced a manic episode.

Adams is back on her old medication and doing fine.

Hockenberry: What do you have to say to the drug company that might have been very interested in doctors prescribing their medication?

Adams: I think that theyre greedy, and they just are after money. And they dont really care about the person who takes the medicine, obviously.

David Franklin says he was surprised how easy it was for him to get doctors to switch to Neurontin or to raise dosages.

Hockenberry: And would they do it?

Franklin: Its remarkable the high percentage of physicians that would do this.

Hockenberry: How did you feel?

Franklin: I would leave a physicians office in pain. There was no other way of describing it. This is,I was in a combination of embarrassed by what I had just done, felt responsibility to the patient, to the doctor and the patient, that I had just misled this individual. And that some third party that wasnt even in the room, some patient, may actually be impacted by it.

Parke-Davis own internal documents obtained by Dateline show the company couldnt have been more excited about: new indications for Neurontin, especially for people like Adams with bipolar disorder: Bipolar disorders offer the greatest expected return on investment as much as $55 million.

Even though the 1995 memo later states there is no pre-clinical evidence of efficacy in bipolar disorders. In other words, no real scientific evidence that it would work. Franklin says the companys enthusiasm about off-label prescriptions translated into real pressure on the job pressure, he says, to sell.

Franklin: I was pressured to fill the gap that the sales team, the actual sales representatives werent filling. That the sales representatives werent as effective as medical liaisons. And that we had to, I think the quote was, to take the ball and run with it.

And Franklin let Dateline experience this sales pressure just as he did, through this recorded voicemail from his boss.

You know theres a Neurontin push thats supposed to be on. So what we need to do is focus on Neurontin, when we get out there we want to kick some ass on Neurontin we want to sell Neurontin on pain all right? And monotherapy I dont know if you guys are embarrassed, but Im embarrassed with where we are with Neurontin.

Franklin saved this voicemail because he could barely believe what his boss was saying: sell Neurontin expressly for uses not approved by the FDA. Franklin was frightened. What he was being asked to do, he believed, was illegal. So he began to tape more conversations and messages from company officials. Heres a quote from a senior Warner-Lambert executive on a conference call:

I want you out there every day selling Neurontin... holding their hand, whispering in their ear, Neurontin for pain, Neurontin for monotherapy, Neurontin for bipolar, Neurontin for everything. I dont want to see a single patient coming off Neurontin before theyve been up to at least 4,800 milligrams a day.

And then he said this:

I dont want to hear that safety crap either. Its a great drug

We showed Assistant U.S. Attorney Jim Sheehan that colorful quote.

Sheehan: It would seem to me thats a pretty clear advocacy for off-label use by the company. And therefore a violation of the FDAs rules.

Hockenberry: You know, I dont know if Id use the word advocacy. I might use, like, threat.

Sheehan: When I look at this, Neurontin not for pain, not an on-label use, Neurontin for bipolar, not approved, no application for that either. Neurontin for everything, well, thats pretty obvious.

And company sales people got to make this pitch right in the inner sanctum of doctors offices. Franklin would tell doctors they could get paid to let company sales reps go over patient medical records and to actually be there in the examining room while patients were being treated.

Franklin: If you are willing to allow a sales representative to spend a day with you as you see patients, well compensate you for that. Well pay you for it.

This is a voicemail Franklin recorded, in which a salesman boasts about his success after a day spent with a doctor and his patients:

The doctor would review the chart of each patient with me in a one-on-one fashion. Then we would go meet the patient, the patient would be examined. I saw the actual prescription generated in front of me... that was certainly nice. I certainly felt that me being there, I had some influence on that medical decision.

Medical decisions that were very good business. From its introduction in 1993, Neurontin the little epilepsy drug, has rocketed to the top of the sales charts. Today its a more than $2 billion drug, outselling even blockbuster Viagra, and more than three-quarters of Neurontins sales, by the parent companys own estimate, are from off-label uses.

But Franklin was having serious doubts about the safety of off-label use, about his job and about what kind of legal trouble he might be in. He would not make it through his first year at Parke-Davis. In the summer of 1996, he decided hed had enough.

GOING PUBLIC

By the early summer of 1996, after four months working as a medical liaison for Warner-Lambert, David Franklin began to realize it was time to get out. He believed what he was doing was wrong and feared what would happen if he stayed.

Franklin: I knew that in the period of time that I had been there, my own personal behavior was illegal, that I had done things that were simply illegal.

His biggest worry was that he was aiding and abetting a medical fraud. The scientist who reluctantly became a salesman now wondered if he had what it took to blow the whistle on a drug company worth billions.

Franklin: Either I needed to own up to this now and put it behind me, or at some point in the future, this could come back, and Id find myself on the wrong side of this investigation. I did believe, when I left, that they were so aggressively ramping this up, that at some point, someone would expose what was going on there. And therefore, I would find myself in the equally, or even more difficult, position of trying to explain why I ignored an obvious illegal and immoral activity within the company.

So on July 29, he drove to a co-workers home, dropped off his office keys and company car and turned his back on Parke-Davis for good. Next stop? Greene and Hoffman attorneys at law.

Franklin: I showed up to their office saying, Ive Im in trouble. And I need some help out of this.

Franklin filed a lawsuit against Warner-Lambert and its Parke-Davis division charging the company with violations of the U.S. False Claims Act. He says he was not motivated by the fact that he stands to be in line for a percentage of the damages if the company loses or if it settles out of court.

Tom Greene: We had no idea the extent of the Neurontin prescriptions, how successful this program had been.

Tom Greene is David Franklins attorney. He has spent the last seven years amassing Warner-Lambert and Parke-Davis documents going back to 1994. He shared many of them with Dateline they fill more than 160 boxes, memos and reports that prove, Greene says, that David Franklin was merely a cog in a grand marketing strategy to deliberately and illegally encourage off-label use.

Greene: There are countless documents that support what he says and go far beyond his story and bring the level of knowledge of this illegal marketing program to the highest levels of the company.

For example, one memo shows that plans for marketing Neurontin for at least one off-label use were sent to top executives, including Anthony Wild, the president of Parke-Davis pharmaceutical division, and Lodewijk de Vink, president of parent company Warner-Lambert. Neither responded to our request for comment.

Other Parke-Davis documents, like one from 1997, show that there were teams inside the company not merely pushing the envelope on acceptable marketing practices but deliberately advocating going around the expensive FDA approval process, because the patent life of the drug was so short.

The recommendation is that Parke-Davis not file an application with the FDA but instead take the message straight to the doctors.

It was a full-court press. While sales reps and medical liaisons like David Franklin supplied company information in doctors offices, documents show company messages being planted aggressively in the scientific literature. Doctors simply trying to stay educated about new drugs would find themselves inundated with research, paid for by the company and made to look like independent scientific papers.

Greene: They wanted to disseminate knowledge of these off-label uses throughout the medical literature. They hired outside companies to write articles about off-label uses so that the message about off-label use of Neurontin could be planted in the medical literature around the country, and indeed around the world.

Heres one example of how what Parke-Davis called its publication strategy worked: A company called Medical Education Systems of Philadelphia (MES) was hired by Parke-Davis to put together a series of articles on off-label uses of Neurontin. MES would contact doctors hand-picked by Parke-Davis to author the articles. But in some cases, it appears that articles were essentially ghostwritten by MES, and the doctors name added later. As one MES status report notes: MES draft completed we just need an author.

And what did the doctors get for becoming authors of papers they sometimes didnt write? Fees of up to one thousand dollars a pop.

Sheehan: You are attempting to create a false impression, and you are making false representations, and youre doing it for money. I just dont see how that approach can be supported or can be viewed as appropriate.

Hockenberry: You know, its always been my impression that the finding of an author precedes the actual writing of the paper.

Sheehan: One would hope thats what would happen.

Papers were just the beginning. Franklin says there was lots of money to go around.

Hockenberry: Did you pay doctors?

Franklin: I personally did not pay physicians. What my responsibility was, was to let physicians know that there was money available to them.

In fact the documents show there were all kinds of ingenious ways for doctors to get paid for an education in the use of Neurontin. For instance, honoraria are fees paid to doctors to hear information or a presentation about Neurontin. Parke-Davis records show that these scientific presentations occurred in some unscientific places: Bus to Yankee Stadium, World Yacht Cruise and Braves Stadium.

Doctors were also recruited for teleconferences, seminars and trips to places like Jupiter Beach, Fla., perhaps better known for golf than for research.

Paying physicians like this, giving them drug company money to listen to information about the products they prescribe, may be legal and common practice in the industry, but to critics like Dr. Arnold Relman, professor emeritus at Harvard and former editor of the New England Journal of Medicine, its a conflict of interest especially in the case of Neurontin.

Relman: What you have is an unproven drug being widely used for difficult problems by doctors who are given a powerful economic incentive to do it, spurred on by a company thats wildly aggressive in its marketing.

After seven years of legal motions and countermotions, Franklins lawsuit is now being scrutinized by the U.S. government and all 50 states to see if government medical programs like Medicaid may have been defrauded into spending millions on improper off-label prescriptions.

And in fact, in recently filed court papers, the Justice Department said that Franklins case has presented evidence of an illegal off-label marketing scheme that is rife with false statements and fraudulent conduct all of which had one intended purpose and result increasing sales

Three years ago, Pfizer bought Warner-Lambert and Parke-Davis, so now the biggest drug company in the world is the defendant in one of the highest-profile cases in the history of the industry. Pfizer officials would not speak on camera but did provide this statement: the events to which you referred are alleged to have occurred well before in some cases years before
Pfizer acquired Warner-Lambert.

Pfizer completed the acquisition of Warner-Lambert in June 2000. It is long-standing policy that Pfizer has not and does not promote its products outside their FDA-approved labeling. We are unable to comment further because of the pending litigation...

But its litigation that will mean little to Regina Adams, who says she will always believe that her experience with bipolar disorder and the drug Neurontin almost ruined her life.

Adams: Now that I look back, and that I know what I know now, I wouldnt have ever taken the drug. I want everybody to know thats taking this drug the truth about it.

Last year the FDA approved the use of Neurontin in the treatment of post herpetic neuralgia, severe nerve pain, in addition to epilepsy. It is still widely prescribed for pain and a variety of other unapproved uses, some of which have been studied and endorsed by scientists and approved for use in other countries.

And as for whistleblower Franklin, he may have escaped legal liability for what he did during his four months with Parke-Davis, but he hasnt escaped his own conscience. He admits he should have known from the start that he was heading down the wrong path.

Franklin: Actually interviewing for this position, I was asked about giving examples of where I had to bend the rules in the past and how I handled that and how comfortable was I working in gray areas.

This case could end up clarifying some of those gray areas and end up costing defendant Pfizer millions of dollars. And theres one more thing. Because his lawsuit is filed under the federal False Claims Act, as a whistleblower Franklin stands to get a piece of any monetary damages, up to 30 percent, which could add up to millions. So the four-month job in sales that caused so much agony for this scientist, ironically, might in the end have set him up for life.

Hockenberry: But even after you get a settlement, if you do, or a judgment if you do, or the case just completely goes away if it does, there are patients out there who took drugs based on decisions doctors made relying on your judgment.

Franklin: Right.

Hockenberry: They could be hurt because of that.

Franklin: They may have been hurt. And thats something that I wrestle with.

Hockenberry: Whats to wrestle with? If theyre hurting, its because of you.

Franklin: Its because of me. There hasnt been a day in six years that I havent thought about this and wrestled with my involvement in it and the guilt I feel associated with it, and the sense that I need to correct it.

US Filing Backs Suit Against Drug Firm

Wed, 28 May 2003 00:00:00 -0700

The US attorney's office in Boston said in court documents that the drug company Parke-Davis, now Pfizer, gave illegal kickbacks to doctors, including trips to Puerto Rico and tickets to the 1996 Summer Olympics, to prescribe what has become the nation's best-selling anticonvulsant, Neurontin.

The Boston office, the country's most aggressive prosecutor of healthcare fraud, has refused to comment on a civil whistle-blower lawsuit filed more than six years ago against Parke-Davis by David Franklin, a former employee. But by filing a ''statement of interest'' in the case Friday, federal prosecutors for the first time outlined their support of Franklin's case and their belief in his allegations that the company engaged in an illegal marketing scheme to increase sales of its epilepsy drug.

Federal prosecutors yesterday declined to comment on the significance of the filing or whether they are planning to file criminal charges against the company. According to documents filed previously in the Franklin case, the US attorney's office in Boston is negotiating a settlement with Pfizer, which purchased Parke-Davis in 2000. Pfizer executives yesterday declined to comment on the government's filing.

Federal and state prosecutors, angry over the soaring costs of prescription drugs to the state and federal Medicaid program, are increasingly investigating and bringing charges against companies that allegedly market drugs illegally. Costs for Neurontin, in particular, have grown dramatically for Medicaid programs, which provide health insurance to the country's poorest residents. Ohio Medicaid spent $24 million on the drug last year, twice what it spent in 2000. Florida's expenditures tripled to $15 million between 1998 and 2001. And Massachusetts spent $25 million on Neurontin last year, compared with $3 million just three years ago.

Most of these payments were not for prescriptions for epilepsy, but for ''off-label'' uses not approved by the US Food and Drug Administration such as bipolar disease and certain types of pain. It is illegal for a pharmaceutical company to promote its drugs for unapproved conditions, though it is not illegal for physicians to prescribe drugs for off-label uses.

In settlement negotiations, prosecutors would aim to recover some of these expenditures under the False Claims Act making fraudulent claims for payment to the government and the Anti-Kickback Statute.

In the filing Friday, federal prosecutors said Franklin and his attorney, ''presented evidence of an illegal off-label marketing scheme that is rife with false statements and fraudulent conduct all of which had one intended purpose and result increasing sales and, therefore, the claims for off-label uses of Neurontin submitted to Medicaid.''

The filing was to oppose Pfizer's request for summary judgment a ruling in its favor without a trial in the case.

Prosecutors said Parke-Davis misled doctors into believing that programs discussing uses for Neurontin were independent educational programs when they actually were marketing efforts led by Parke-Davis. For example, prosecutors said, Parke-Davis joined in an undisclosed relationship with a company known as Physicians World where Parke-Davis employees transferred to Physicians World to run Parke-Davis's speakers bureau.

At the same time, prosecutors said, a division of Physicians World, known as Professional Post-Graduate Services, purported to be an independent medical education provider that created a program on anticonvulsants for pain, but did not say that Parke-Davis staff planned and developed the program. Thousands of US doctors took the classes.

The US attorney's office said the company gave doctors kickbacks in the form of lavish trips and tickets disguised as educational or consulting payments. In one instance, prosecutors said, Parke-Davis paid for doctors to stay five days in Atlanta during the 1996 Summer Olympics. The doctors stayed at the Chateau Elan Resort and Winery, and the company covered their meals, use of the resort, and motorcoach travel to the games. Agendas for the meeting listed 10.5 hours of business meetings, including one session devoted to off-label uses for Neurontin, prosecutors said.

The government argued that in setting up the Medicaid program, Congress depended on the integrity of doctors' decisions in prescribing drugs, and that it is vital the process ''be untainted by self-interest or improper inducement.''

''For the programs to function in the best interests of public welfare individual patient health as well as the continued fiscal viability of the programs they must function free of the insidious effects of kickbacks and related financial conflicts of interest,'' wrote US Attorney Michael Sullivan and Assistant US Attorney Sara Miron Bloom.

Ruling Sought Against Pfizer: Federal Prosecutors Say Anticonvulsant Marketed Illegally

Sun, 18 May 2003 00:00:00 -0700

Federal prosecutors yesterday accused drug company Parke-Davis, now Pfizer Inc., of a widespread and fraudulent scheme to persuade doctors to prescribe what has become the country's top-selling anticonvulsant, Neurontin.

Assistant US Attorney Sara Miron Bloom's comments came during a hearing yesterday in US District Court in Boston and represent the government's growing interest in a civil whistle-blower lawsuit filed more than six years ago against Parke-Davis by David Franklin, a former employee.

Bloom said Franklin and his lawyers had presented substantial evidence that the company made false statements to doctors, including telling them that federal regulators had approved Neurontin for stand-alone treatment for epilepsy when regulators had in fact rejected the drug for that use. Neurontin is approved only as an add-on drug for epilepsy and for a certain type of pain.

Bloom asked US District Judge Patti Saris to reject Pfizer's request for summary judgment a ruling in its favor without a trial in the case. The US Attorney's Office in Boston is currently in settlement negotiations with the company to recoup money the state and federal Medicaid program spent on Neurontin for Medicaid recipients.

Franklin's attorney, also asked the judge to rule against Pfizer.

But Pfizer attorneys argued that the whistle-blower had not made his case, saying that even though Greene showed that nine doctors increased their Neurontin prescribing for unapproved uses after they attended Parke-Davis dinners or trips, he did not interview the doctors or prove the company's event caused them to prescribe more of the drug. The company's attorneys also said Greene failed to prove that the payments to doctors for consulting and other services were kickbacks specifically intended to sway them into using more Neurontin, and have in previous court filings denied the allegations in the case.

Bloom, however, said the company continually promoted the drug to doctors for unapproved uses which is not allowed under federal law by paying them to attend meetings as consultants, through sales representatives in their offices, by sponsoring continuing medical education courses without disclosing the company's financial backing, and by inviting physicians on ''trips and boondoggles.'' She said this off-label promotion resulted in increased payments for the drug by the state and federal Medicaid program for the poor.

Physicians recorded many of the sales representatives' statements about unapproved uses in slips they filled out for a company called Verispan, which tracks the effectiveness of sales calls for pharmaceutical companies including Parke-Davis.

Federal and state prosecutors, angry over the soaring costs of prescription drugs to Medicaid, are increasingly investigating and bringing charges against companies that allegedly market drugs illegally. Costs for Neurontin, in particular, have grown dramatically for Medicaid programs, which provide health insurance to the country's poorest residents. Ohio Medicaid spent $24 million on the drug last year, twice what it spent in 2000. Florida's expenditures tripled to $15 million between 1998 and 2001. And Massachusetts spent $25 million on Neurontin last year, compared to $3 million three years ago.

Drug Firm Pfizer Suspected of Illegal Marketing

Sun, 20 Oct 2002 00:00:00 -0700

The Washington state Attorney General's Office is leading a national investigation into whether a drug company illegally marketed an epilepsy medication called Neurontin.

Assistant Attorney General David Waterbury, based in Tacoma, is leading the investigation on behalf of 47 states and the District of Columbia, he said in an affidavit filed last week in U.S. District Court in Boston.

He's investigating whether Pfizer marketed Neurontin for "off-label" uses meaning for uses that the U.S. Food and Drug Administration has not approved.

It's legal for doctors to prescribe drugs for off-label purposes for example, prescribing an anti-seizure drug to treat a sleep disorder. But it's illegal for drug companies to market them that way.

Washington Medicaid spending on Neurontin increased more than tenfold from 1996 to 2000, the height of the marketing campaign.

The Boston Globe reported that Massachusetts' medical director for Medicaid is reviewing the growing number of Neurontin prescriptions for mood disorders, bipolar illness and sleep problems.

Waterbury's investigation could lead to criminal, civil or administrative charges, he said Friday. He said the allegations are "very significant."

Calls to three Pfizer spokespeople were not returned Friday.

In 1996, a whistle-blower doctor started a civil lawsuit against Parke-Davis and Pfizer in U.S. District Court in Boston. That lawsuit is ongoing, and the U.S. Attorney's Office in Boston is conducting a criminal investigation.

Hundreds of pages of Parke-Davis internal records were released by the court last May, The Globe reported, revealing a marketing strategy for off-label use of Neurontin that included ghostwriting journal articles for doctors and rewarding potential prescribers with beach trips.

Waterbury filed his affidavit in response to the U.S. District Court's request for information about the Medicaid investigation.

The state is not a party to the suit.

Neurontin was created and marketed by Parke-Davis, which merged with Pfizer two years ago. Waterbury also is investigating how much the drug's marketing influenced Medicaid spending on Neurontin.

The Globe reported that Medicaid spending on the epilepsy drug in Massachusetts increased from $1 million in 1996 to $14 million in 2000.

Neurontin Suicide Side Effects Lawyer

Sun, 20 Oct 2002 00:00:00 -0700

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Injured by Neurontin?

Neurontin Suicide Link
Neurontin (Generic: Gabapentin) may be linked to suicide and suicide attempts. Neurontin is prescribed for epilepsy but has been prescribed for numerous off label uses. Neurontin was approved for sale in the mid-1990s as a treatment for epileptic seizures. However, it is believed that about 80% of all Neurontin prescriptions are written for conditions other than what the drug was approved to treat.

Neurontin Off Label Prescriptions
It is believed that Parke-Davis, which was acquired by Pfizer in 2000, had a systematic strategy to market and promote Neurontin for untested uses, such as chronic pain, bipolar disorder and migraines. It is not illegal for a doctor to prescribe a drug for conditions outside of those it was approved for, however it is illegal for a drug company to market a medication for off label uses. In July 2003, Dateline aired an investigation which accused Parke-Davis of deliberately falsifying medical information about Neurontin so doctors would prescribe the drug off label to treat a multitude of conditions. State and Federal prosecutors have launched investigations into the allegedly illegal marketing of Neurontin. In its year-long investigation, Dateline interviewed a former Parke-Davis scientist who alleges company officials encouraged him to persuade physicians to prescribe Neurontin for a number of disorders, including attention deficit disorder and bipolar disease, even though there was minimal preliminary data indicating that Neurontin could help patients with those diseases.

In May 2003, The U.S. attorney's office in Boston said in court documents that the drug company Parke-Davis, now Pfizer, gave illegal kickbacks to doctors, including trips to Puerto Rico and tickets to the 1996 Summer Olympics in exchange for prescribing the anticonvulsant Neurontin. Below is a list of the off-label conditions that Neurontin was marketed to treat. These 11 uses were never submitted to the Food & Drug Administration (FDA) for approval, yet illegally promoted.

Bipolar Disorder
Pain Syndromes, Peripheral Neuropathy, and Diabetic Neuropathy
Treatment of Epilepsy alone (as monotherapy)
Reflex Sympathetic Dystrophy (RSD)
Attention Deficit Disorder (ADD)
Restless Leg Syndrome (RLS)
Trigeminal Neuralgia
Post-Hepatic Neuralgia (PHN)
Essential Tremor Periodic Limb Movement
Migraine
Drug and Alcohol Withdrawal Seizures

If you or a loved one took Neurontin and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.