Pfizer Admits Guilt in Promotion of Neurontin–Agrees to Pay $430 Million

Pfizer Admits Guilt in Promotion of Neurontin–Agrees to Pay $430 Million

Sun, 16 May 2004

A lawsuit initiated by Dr. David Franklin, a whistleblower, has been settled: Pfizer pleaded guilty to criminal fraud in the promotion of Neurontin, and agreed to pay $430 million. This case is but an example of contemporary drug marketing, demonstrating that the current system–as overseen under the stewardship of the FDA–encourages rather than discourages fraudulent marketing of ineffective, even dangerous drugs.

Neurontin was approved for limited use as a supplemental anti-seizure treatment for epilepsy, but was promoted by Lambert-Warner (now Pfizer) and a consortium of paid physicians who promoted and prescribed the drug for everything from ADHD, mental illnesses to a variety of pain conditions, including migraine headaches. The Wall Street Journal reports (below): “use of Neurontin for unapproved uses – estimated to account for 90% of the $2.7 billion in sales last year – continues to rise despite stepped up prosecutorial efforts aimed at curbing the practice. At the same time, studies show that much of the unapproved use of Neurontin isn’t even effective.”

The commercially successful marketing “miracle” of Nuerontin was achieved through a collaborative effort of the company and leading physicians who were given financial incentives to encourage their colleagues–under the pretext of providing “continuing medical education”–to prescribe a largely ineffective drug for unapproved, diverse and unrelated conditions. Essentially physicians were “educated” to use their prescribing license to increase profits rather than to improve their patients’ health. The Wall Street Journal reports that studies have found off-label use accounted for 40% to 50% of all prescriptions.

In much the same way that Neurontin was promoted, manufacturers of SSRI antidepressant drugs have promoted these drugs for an array of loosely defined “disorders” and off-label uses. The promotional tactics that made Pfizer’s drug, Zoloft (and the other antidepressants) commercial blockbusters are not very different from the tactics used to promote Neurontin. The commercial success of antidepressants was achieved through the collaborative effort of the manufacturers and a consortium of leading psychiatrists, academic institutions (including the National Institute of Mental Health), and professional associations–such as, the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry, among others.

The leading opinion shapers in psychiatry all have substantial financial conflicts of interest. They receive grants, stipends (which are sometimes disguised as post-marketing research grants), and perks (honorariums) from drug manufacturers–and some psychiatrists own stocks in the companies. Furthermore, academic institutions that conduct industry-sponsored drug trials, as well as the NIMH, collaborate with industry on “public awareness” campaigns that are disguised marketing campaigns.

See: Emory University, GlaxoSmithKline, and National Institute of Mental Health. Create Partnership To Develop New Treatments for Depression Monday, 1 December 2003. http://www.eurekalert.org/pub_releases/2003-12/euhs-egn120103.php

See: APA Allies and National Campaigns, http://www.psych.org/public_info/allies2.cfm

Opinion leaders in psychiatry have promoted SSRIs for children–even as the evidence from company controlled trials demonstrates, the drugs are neither safe nor effective. See: Koplewicz, H. “Misguided Resistance to Appropriate Treatment for Adolescent Depression” Editorial, Journal of Child & Adolescent Psychopharmacology, 2004.

*See: Peter R. Breggin. Suicidality, violence and mania caused by SSRIs: A review and analysis. International Journal of Risk & Safety in Medicine 16 (2003/2004)

Leading child psychiatrists have, in large part, debased the scientific literature by penning their name to ghostwritten reports that promote unsupportable, off-label prescribing of antidepressants for children.

*See: Jon N Jureidini, Christopher J Doecke, Peter R Mansfield, Michelle M Haby, David B Menkes, Anne L Tonkin, Efficacy and safety of antidepressants for children and Adolescents, British Medical Journal, online free at: http://bmj.bmjjournals.com/cgi/content/full/328/7444/879?

*See: Craig J Whittington, Tim Kendall, Peter Fonagy, David Cottrell, Andrew Cotgrove, Ellen Boddington. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. The Lancet. Volume 363, Number 9418, April 24, 2004, online free at: http://www.thelancet.com/journal/journal.isa

Pfizer agreed to pay a fine of $430 million for its Neurontin marketing tactics. The doctors, however, have not been charged with a crime. The punishment is unlikely to discourage corrupt practices in an industry with annual sales of $216 billion. The New York Times reports: “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.” See: Harris, G. Pfizer to Pay $430 Million Over Promotion of Drug by Gardiner Harris, NYT, May 14, 2004, C-1. Indeed, The Wall Street Journal reports that studies have found off-label use accounted for 40% to 50% of all prescriptions.

The New York Times reports: “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.” See: Harris, G. Pfizer to Pay $430 Million Over Promotion of Drug by Gardiner Harris, NYT, May 14, 2004, C-1.

The FDA has failed to use its authority to enforce the law to protect the public health. Instead the FDA has supported drug companies in cases involving false advertising and failure to disclose hazardous risks. In September 2002, the Chief Counsel of the FDA filed an Amicus Curiae brief in support of Pfizer in a case charging Pfizer with failure to warn that the antidepressant, Zoloft, poses a suicide risk. The FDA brief asserted that Pfizer did not have to warn physicians about the suicide risk because there was no evidence of a causal relationship. The law does not require proof of a causal relationship. The law requires prominent warnings whenever there is “reasonable evidence of a possible association of the drug with a serious health hazard.” See: 21 C.F.R. §§201.57(e).

The FDA brief also misrepresented the purpose of federal regulations, stating: “FDA’s regulation of prescription drugs is designed to ensure each drug’s optimal use” claiming that “under-utilization of a drug… could well frustrate the purposes of federal regulation.” (p. 23) This statement in a document submitted by the FDA to a court of law contradicts the legal parameters of legitimate vs. fraudulent drug promotion. The purpose of FDA’s regulation is to protect the public from undisclosed drug hazards, not to maximize profits–i.e, “ensure the drug’s optimal use.” See: Motus v Pfizer. 2002. U.S. Court of Appeals, 9th Dist. FDA Amicus Curiae brief in support of Defendant (Pfizer), in favor of reversal of the District Court.

If the promotional claims about the efficacy and safety of Neurontin were backed up by scientific evidence, Pfizer would not have pled guilty of fraud. Similarly, the promotional claims for antidepressants are not backed by evidence. Indeed, since the Motus suit, the FDA acknowledged the suicidal risk of the drug. See: http://www.fda.gov/cder/drug/antidepressants/AntidepressanstPHA.htm

Under the current system, nothing prevents pharmaceutical companies from offering financial incentives to physicians; nothing prevents physicians from misusing their prescribing licenses to increase drug sales. As a result, healthy children have been exposed to harmful drugs, and the cost of drugs has skyrocketed. Unless Congress creates an oversight agency for the biomedical and healthcare industry, with legislative authority equivalent to the Securities and Exchange Commission, fraudulently promoted drugs will undermine public health and deplete public budgets.

Contact: Vera Hassner Sharav
Tel: 212-595-8974
e-mail: veracare@ahrp.org

Pfizer Case Signals Tougher Action On Off-Label Drug Use

By DAVID ARMSTRONG and ANNA WILDE MATHEWS
THE WALL STREET JOURNAL
May 14, 2004; Page B1

Although a unit of Pfizer Inc. agreed to plead guilty and pay hundreds of millions of dollars in fines to settle charges of illegal marketing of its drug Neurontin, lawyers in the case doubt it will curb such “off-label” use of the drug.

Indeed, use of Neurontin for unapproved uses — estimated to account for 90% of the drug’s $2.7 billion in sales last year — continues to rise despite stepped-up prosecutorial efforts aimed at curbing the practice. At the same time, studies show that much of the unapproved use of Neurontin isn’t even effective.

The Pfizer case — and others in the works — signal federal regulators’ heightened interest in cracking down on overt promotion of off-label drug use.

Other agencies investigating off-label use include the inspector general for the Office of Personnel Management, the agency that oversees benefits for federal employees. The agency has subpoenaed records from Johnson & Johnson’s Janssen unit related to sales and marketing of the drug Risperdal; from Wyeth, of Madison, N.J., from and Bristol-Myers Squibb Co., New York, according to disclosures made by the companies.

Meanwhile, the U.S. attorney’s offices in Boston and Philadelphia are conducting several off-label investigations. Schering-Plough Corp., Kenilworth, N.J., has indicated it expects to be indicted on federal charges stemming from an investigation by the Boston office into billing and marketing practices.

A big reason health experts and regulators want to curb off-label drug use is that so often such treatment doesn’t work and only adds to health-care inflation. “Every taxpayer in the country has been paying for these prescriptions for minimal benefit to a huge majority of patients,” says Thomas Greene, lawyer for the drug industry whistleblower who brought the Neurontin case to regulators’ attention.

David Franklin, the former drug company employee who first exposed the Neurontin marketing campaign in a 1996 whistleblower lawsuit, said much of the off-label use is to treat conditions in which Neurontin has little or no effect. He said he continues to worry about people who take the drug for unapproved uses.

“Even to this day, the huge majority of people are taking Neurontin” for off-label uses, he said. As for whether the settlement will change the prescribing patterns for Neurontin, Mr. Franklin said it was too early to know.

“People say congratulations, but that is premature,” he said. “A couple of years from now if we see some real change that is when we can deem that this case is truly successful.”

While doctors are free to treat patients with off-label prescriptions, drug companies are restricted in how they promote their products for such unapproved uses. Last year, when total U.S. prescription-drug spending was about $216 billion, studies found off-label use accounted for 40% to 50% of all prescriptions.

ANOTHER PURPOSE

Some drugs that are prescribed for uses not approved by the FDA:

Drug Indicated Use Off-label Use

Abilify Antipsychotic Bipolar disease Beta-blockers Hypertension Performance anxiety, migraine prevention

Prozac Antidepressant Premature ejaculation

Risperdal Antipsychotic Agitation in elderly

Topamax Antiepileptic Weight loss

Zoloft Antidepressant Bulimia

Source: Decision Resources Inc.

But doctors also maintain that in some cases, off-label prescribing is good medical practice. For instance, many medications approved to treat specific cancers have proved effective when prescribed for other forms of cancer.

In the case of Neurontin, originally approved as a supplemental antiseizure treatment for epilepsy, doctors have embraced the drug to treat migraines, mental illness and a variety of pain conditions. Many of the doctors originally were persuaded to try the drug for these uses between 1996 and 2000 by sales people from Warner-Lambert, a company that Pfizer took over.

Now that doctors are in the habit of issuing such prescriptions, no one expects them to change their practices. A small part of yesterday’s $430 million settlement — $38 million — will go toward educating consumers and doctors about the potential hazards of off-label usage, but that’s only a fraction of what drug companies spend on marketing.

The settlement, announced in Washington yesterday, punishes Pfizer and its Warner-Lambert unit for off-label sales of the drug to Medicaid, the federal insurance program for the poor.

Asked about the widespread off-label use of Neurontin, Pfizer spokesman Paul Fitzhenry said, “I don’t see where that would change.” Pfizer has declined to give an estimate of how much of the drug’s use is off-label.

The U.S. Attorney in Boston, Michael Sullivan, said he didn’t know if Neurontin sales would be curbed by the settlement, but acknowledged the drug “has a pretty significant base.” The settlement also contains a corporate responsibility agreement dictating how Pfizer should market and promote its products, but the company said it already adheres to those guidelines.

Pfizer said all of the activities in question occurred before it acquired Warner-Lambert in 2000. It said none of its sales people promote off-label drug use.

The Neurontin case was closely watched because drug companies, long accustomed to Food and Drug Administration scrutiny over advertising practices, have seen the Justice Department becoming far more aggressive in cracking down on off-label promotion. In the past year, at least seven drug companies have been served with subpoenas related to off-label marketing.

Earlier FDA efforts to crack down on off-label advertising were hamstrung by court decisions holding that certain types of drug promotions were protected by the First Amendment. As a result, companies believe they have a “safe harbor” from the FDA for some forms of off-label promotion, including providing doctors with medical-journal articles and textbooks that support use of their drugs in ways not authorized on the labels. In addition, the FDA’s current leadership is widely seen as taking a cautious approach to enforcement that could run afoul of courts’ interpretation of constitutional protection for free speech. A spokesman says the FDA helped with the Neurontin case and continues to go after companies that violate its off-label advertising rules.

The recent stepped-up activity by U.S. attorneys “sent alarm bells through” the drug industry, says Peter Barton Hutt, a lawyer and former top FDA official who now has drug companies as clients. Before the Justice Department’s recent series of investigations, “we all thought we knew where the lines were at FDA, and they had become more flexible.”

Warner-Lambert agreed to plead guilty to two counts of violating the Food, Drug and Cosmetic Act and pay a $240 million criminal fine. It will also pay $83.6 million in civil damages for losses suffered by Medicaid, and $68.4 million to settle civil liabilities for the losses to state Medicaid programs, according to Justice Department officials.

Warner-Lambert also will pay $38 million in civil penalties for harm caused to consumers and fund a remediation program to address the effect of its improper marketing. Mr. Franklin, the whistleblower, will be paid $26.6 million from the federal settlement amount.

–Sara Schaefer Muñoz contributed to this article.

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