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By Herb Newborg

Pfizer Engages in Rampant Research Fraud
Pfizer rigged studies and then used the ill-gotten results to commit further crimes.

Pfizer engaged in rampant research fraud in company-sponsored studies of the anti-seizure drug Neurontin for off-label uses, researchers have suggested. Pfizer concealed evidence the epilepsy drug Neurontin didn't work for those unapproved uses, including nerve pain, migraines and bipolar disorder according to a new report. When a company-funded study's primary finding wasn't favorable, that result was usually buried and something else positive was highlighted, without disclosing the switch.

What did Pfizer do with the cooked research data? Despite the fact that Neurontin was only approved as an adjunctive therapy for epilepsy, it was widely and illegally promoted by Pfizer for pain. They hired a consortium of paid physicians who promoted and prescribed the drug for everything from ADHD and mental illnesses to a variety of pain conditions, including migraine headaches. The Wall Street Journal reported in 2004: “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.”

We reported earlier that this drug, widely prescribed off-label for pain, particularly nerve pain, is suspected of increasing suicide and suicidal thoughts.

The commercially successful marketing “miracle” of Neurontin 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.

Earlier this year, we also reported that the key researcher for many of the company sponsored studies of Neurontin stands accused of fabricating results in at least 21 published studies and, in some cases, even inventing patients.

Apparently, in most of the studies that were actually carried out, the results were manipulated. Eight of 12 studies published over a 15-year span reported primary outcomes that differed from those specified in the original trial protocols, said Kay Dickersin, PhD, of Johns Hopkins University, and colleagues.

The researchers reviewed internal documents from Pfizer and its Parke-Davis unit on 20 Neurontin trials, which became public as a result of litigation against the firms. Eight of the studies were never published.

"All the changes that took place between what was specified in the protocol, what was known before publication (as presented in the internal company research reports), and what was reported to the public led to a more favorable presentation in the medical literature of Neurontin's efficacy for unapproved indications. We were concerned that the reporting practices observed in our analysis did not meet the ethical standards for clinical research or maintain the integrity of scientific knowledge"," Dickersin and colleagues said.

This type of research fraud by pharmaceutical companies is far from rare. Earlier this week, a study in Annals of Family Medicine found that trial outcomes often change between original design and published report. The primary outcomes of nearly a third of randomized trials, as published in five top journals, differed from those previously indicated in clinical trial registry listings.

Dr. Sidney Wolfe, head of health research at consumer group Public Citizen, called this latest report the first comprehensive look "at studies in which a company and people working for it so maliciously manipulated the data to make a drug look more effective than it actually was."

"In every instance, the published article made the drug look better than it would have," said Wolfe, a member of the Food and Drug Administration's drug safety advisory committee. "This results in harm."

The Neurontin trials examined the drug for prevention of migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain. None of these are currently approved indications for Neurontin, but the drug is now approved for postherpetic neuralgia and is believed to be widely prescribed off-label for many other types of pain.

Continued litigation for criminal activity by the drug manufacturer is what led to the availability of the reviewed documents that have uncovered this latest fraud.

Dickersin got the documents while serving as an expert witness against Pfizer, which in 2004 paid $430 million to settle civil and criminal charges regarding the illegal marketing of Neurontin for off-label purposes. Further legal action is pending on that case. Neurontin, part of Pfizer's product line now, had sales of $387 million in 2008 (since it is now available in a generic form) and is estimated to be used by around 12 million people in 60 countries since its introduction in 1994.

Pfizer was sued again last year by lawyer Thomas Greene, who brought the original case against the company for off-label marketing practices, for holding back negative study results and changing the design of its trials to produce more favorable results.

That case was the latest in a string of allegations against the pharmaceutical industry, particularly Pfizer, suggesting it has controlled the flow of clinical trial research to boost its marketing position.

Prosecutor Michael Loucks, in a recent interview with Bloomberg, recalled clearly when lawyers for Pfizer looked across the table and promised it wouldn’t break the law again.

This was January 2004, and the attorneys were negotiating in a conference room on the ninth floor of the federal courthouse in Boston, where Loucks was head of the health-care fraud unit of the U.S. Attorney’s Office working to settle the case against Pfizer’s units for pushing doctors to prescribe Neurontin for uses the Food and Drug Administration had never approved.

In the agreement the lawyers eventually hammered out, the Pfizer unit, Warner-Lambert, pleaded guilty to two felony counts of marketing a drug for unapproved uses.

Pfizer agreed to pay the $430 million in criminal fines and civil penalties mentioned above, and the company’s lawyers assured Loucks and three other prosecutors that Pfizer and its units would stop promoting drugs for unauthorized purposes.

What Loucks, who’s now acting U.S. attorney in Boston, didn’t know until years later was that Pfizer managers were breaking that pledge not to practice so-called off-label marketing even before the ink was dry on their plea.

On the morning of Sept. 2, 2009, another Pfizer unit, Pharmacia & Upjohn, agreed to plead guilty to the same crime. This time, Pfizer executives had been instructing more than 100 salespeople to promote Bextra, a drug approved only for the relief of arthritis and menstrual discomfort, for treatment of acute pains of all kinds.

For this new felony, Pfizer paid the largest criminal fine in U.S. history: $1.19 billion. On the same day, it paid $1 billion to settle civil cases involving the off-label promotion of Bextra and three other drugs with the U.S. and 49 states.

“At the very same time Pfizer was in our office negotiating and resolving the allegations of criminal conduct in 2004, Pfizer was itself in its other operations violating those very same laws,” Loucks, 54, says. “They’ve repeatedly marketed drugs for things they knew they couldn’t demonstrate efficacy for. That’s clearly criminal.”

The penalties Pfizer paid this year for promoting Bextra off-label were the latest chapter in the drug’s benighted history. The FDA found Bextra to be so dangerous that Pfizer took it off the market for all uses in 2005.

The total of $2.75 billion Pfizer has paid in criminal fines and penalties since 2004 may seem significant. However it is a little more than 1 percent of the company’s revenue of $245 billion from 2004 to 2008.