Drug giant accused of false claims
Whistleblower alleges illegal encouragement of off-label use
By Melody Petersen
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Newly unsealed court documents reveal that some physicians, in exchange for money, have allowed pharmaceutical sales representatives into their examining rooms to meet with patients, review medical charts and recommend what medicines to prescribe.
And some of those salespeople tried to influence doctors to prescribe drugs for uses that were not approved by the federal Food and Drug Administration, those documents show.
This so-called shadowing program, apparently involving hundreds of patients, is just one way that Warner-Lambert tried to increase sales of a drug called Neurontin, not just for epilepsy, for which it was approved, but also for more than a dozen medical conditions it was never approved to treat, according to a federal whistle-blower case that is now the subject of a criminal and civil investigation by the United States attorney's office in Boston.
The case details marketing practices that experts say have become standard practice for many pharmaceutical companies as they spend billions of dollars trying to persuade physicians to prescribe their drugs. A recent survey of physicians in Maryland, for example, found that 37 percent said they had accepted some kind of compensation from pharmaceutical companies.
According to court documents, Warner-Lambert, which has since been acquired by Pfizer, tracked whether doctors prescribed Neurontin, rewarding those who were considered high-volume prescribers by paying them as speakers and consultants and also paying them to enter patients in clinical trials.
Warner-Lambert also tried to influence doctors who wrote medical journal articles about Neurontin by paying them, sometimes secretly, and even hiring a marketing company to write first drafts. The drug is expected to reach $2 billion in sales this year.
Dr. Marcia Angell, the former editor of The New England Journal of Medicine, said having sales representatives tell doctors what to prescribe while examining patients was "inexcusable."
"Drug companies have no business being involved in education or clinical care," she said.
In the case of Warner-Lambert, one sales representative boasted that he had persuaded a doctor to prescribe Neurontin for unapproved uses, according to a voice-mail message obtained by the whistle-blower. "While the patient was dressing, the doctor and I one-on-one would discuss the patient and therapeutic options," the sales representative said. "I felt I had influenced her."
The lawsuit, brought by Dr. David P. Franklin, a former Warner-Lambert employee, is based on thousands of pages of internal company documents. The documents do not reveal whether doctors told their patients who the third person was in the examining room.
Dr. Franklin accuses Warner-Lambert's sales representatives of encouraging doctors to experiment by prescribing Neurontin for unapproved uses including pain, bipolar disorder and attention deficit disorder in children.
It is illegal for a drug company to promote a medicine for uses not approved by the government, though it is not illegal for doctors to prescribe medicines for so-called off-label uses.
Warner-Lambert's shadowing program involved an estimated 75 to 100 doctors in several Northeast states, Dr. Franklin estimated in court documents. Each doctor was paid $350 or more for each day they let sales representatives watch as they examined patients, according to court documents.
Other companies also pay doctors to open their doors to sales people.
The federal investigation, which stems from the whistle-blower lawsuit, centers on marketing activities that took place in the mid- to late-1990's, before Pfizer bought Warner-Lambert in 2000. The lawsuit argues that Medicaid paid tens of millions of dollars it should not have for Neurontin prescriptions written for unapproved uses.
Pfizer said that in 2000 more than 78 percent of Neurontin prescriptions were written for unapproved uses. Sales of the drug are growing at a rate of 50 percent a year - fueled mostly by those off-label uses.
Neurontin has been approved by the F.D.A. for a very narrow use: controlling seizures in epileptics who already take another drug. But one marketing executive at Warner-Lambert, in a recorded voice-mail message that is part of the lawsuit, told sales representatives: "If we are going to market Neurontin effectively, we have to do it for monotherapy, for epilepsy, also for pain and bipolar and other psychiatric uses." (Monotherapy refers to using a single drug to treat a condition, which is not an approved use of Neurontin.)
But researchers working independently from the company say they are finding that Neurontin does not work for some of those unapproved uses cited in the lawsuit. In a few cases, these researchers say, Neurontin may make patients worse.
Dr. Jessica Wehner Lea and other doctors at the Northwest Missouri Psychiatric Rehabilitation Center said they recently had found that some patients taking Neurontin for schizophrenia or bipolar disorder appeared to become more aggressive after starting on the drug.
"Neurontin is being used like water for disorders where there is not much evidence it is effective," said Dr. Jonathan Sporn, clinical fellow in the mood and anxiety program at the National Institute of Mental Health. Dr. Sporn led a clinical trial funded by the government that showed that Neurontin worked no better than a sugar pill for patients with obsessive-compulsive disorder.
Many doctors, however, say that Neurontin appears to help some patients with pain. Last year, eight years after Neurontin was put on the market, Pfizer filed data with the Food and Drug Administration from clinical studies to try to gain approval for the medicine's use for pain.
In his first public interview since filing the whistle-blower case, Dr. Franklin, a 40-year-old former research fellow at Harvard Medical School, said that soon after joining the company in 1996 he was asked to participate in what he now says was an illegal marketing scheme that put patients at risk.
Dr. Franklin said he was most troubled by the company's insistence that he press doctors to prescribe Neurontin in much higher doses than had been approved. "It was untried ground," Dr. Franklin said. "We were not sure what would happen at these high doses. I recognized that my actions may be putting people in harm's way."
Dr. Franklin said several Warner-Lambert marketing executives had told him that because Neurontin appeared to be safe in high doses it was reasonable to encourage doctors to try it for almost any neurological condition "just to see what happens."
Dr. Franklin's lawsuit also accuses the company of paying dozens of doctors to speak about Neurontin to their peers - some earning tens of thousands of dollars a year. One internal memo listed doctors the company considered to be "movers and shakers," including some at prestigious medical schools such as Harvard, Cornell and Columbia.
Warner-Lambert also hired two marketing firms to write articles about the unapproved uses of Neurontin and find doctors willing to sign their names to them as authors. According to an invoice from one of the marketing firms, Warner-Lambert agreed to pay the firm $12,000 to write each article and $1,000 to each doctor willing to serve as author.
Internal memos filed in court detail how the marketing firm often wrote a first draft of an article, but sometimes had problems finding an author. The articles were then reviewed and approved by Warner-Lambert before they were sent to journals for publication, records show.
Other drug companies also use marketing firms to help them "ghost write" medical studies, a practice that angers editors of the leading medical journals.
"It is a form of marketing, although it is disguised not to look like marketing," said Dr. Frank Davidoff, the former editor of the Annals of Internal Medicine. "Authors should be authors and should not be signing on to work by someone else, particularly not for money."
Dr. Franklin, the whistle-blower, now works as director of market research at Boston Scientific, a developer and marketer of medical devices. He resigned from Warner-Lambert only a few months after being hired, and said some company executives had threatened to make him a scapegoat if he went public with his concerns.
"I was terrified," said Dr. Franklin, who sought help from Thomas M. Greene, a lawyer in Boston. Dr. Franklin filed his suit several months later.
New York Times May 15, 2002
Follow up story May 30, 2003