Neurotin

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Hi,

I thought many of you might be interested in this.

A lawsuit initiated by Dr. lin, 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, GlaxoKline, 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: 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, J Doecke, R Mansfield, M

Haby, 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, Fonagy, Cottrell,

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: , G. Pfizer to Pay $430 Million Over Promotion of Drug by

Gardiner , 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: , G. Pfizer to Pay $430 Million Over Promotion of Drug by

Gardiner , 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:

e-mail: veracare@...

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 &

'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

Greene, lawyer for the drug industry whistleblower who brought the

Neurontin case to regulators' attention.

lin, 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. lin 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

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, 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 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. lin, the whistleblower, will be paid $26.6

million from the federal settlement amount.

--Sara Schaefer Muñoz contributed to this article.

Write to Armstrong at david.armstrong@... and Wilde Mathews

at anna.mathews@...

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