Healthy Skepticism Library item: 331

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Armstrong D.
Pfizer Case Signals Tougher Action On Off-Label Drug Use
The Wall Street Journal 2004 May 14

Full text:

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.