Experts Conclude Pfizer Manipulated Studies (Published 2008)

• Oct. 8, 2008

The drug maker Pfizer earlier this decade manipulated the publication of scientific studies to bolster the use of its epilepsy drug Neurontin for other disorders, while suppressing research that did not support those uses, according to experts who reviewed thousands of company documents for plaintiffs in a lawsuit against the company.

Pfizer’s tactics included delaying the publication of studies that had found no evidence the drug worked for some other disorders, “spinning” negative data to place it in a more positive light, and bundling negative findings with positive studies to neutralize the results, according to written reports by the experts, who analyzed the documents at the request of the plaintiffs’ lawyers.

One of the experts who reviewed the documents, Dr. Kay Dickersin of the Johns Hopkins Bloomberg School of Public Health, concluded that the Pfizer documents spell out “a publication strategy meant to convince physicians of Neurontin’s effectiveness and misrepresent or suppress negative findings.”

Pfizer issued a statement Tuesday denying that it had manipulated Neurontin data, saying “study results are reported by Pfizer in an objective, accurate, balanced and complete manner, with a discussion of the strengths and limitations of the study, and are reported regardless of the outcome of the study or the country in which the study was conducted.”

The expert reports, unsealed Monday in a federal court in Boston, add to accusations that the pharmaceutical industry has controlled the flow of clinical research data, blurring the lines between science and marketing.

In April, for example, a group of academic doctors questioned the validity of drug industry research after finding that Merck had hired ghostwriters to produce scientific articles about Vioxx, then recruited prestigious doctors to serve as their official authors. Vioxx, a painkiller, was withdrawn from the market in 2004 after research indicated it could cause strokes and heart attacks.

Last winter, Merck and Schering-Plough were criticized for delaying the release of a study on their best-selling cholesterol medication Vytorin that showed the drug did not slow the growth of plaque in arteries. In the case of Pfizer’s Neurontin, the negative studies would have increased doubts about the drug’s value for several unapproved uses — treating bipolar disorder, controlling certain types of pain and preventing migraine headaches, according to the expert opinions.

So-called off-label use of Neurontin for those conditions helped propel its sales to nearly $3 billion a year before it lost patent protection in 2004.

In one example, the experts concluded that Pfizer had deliberately delayed release of a study that showed the drug had little effect against pain that is a complication of long-term diabetes, even as the outside researcher who was a lead investigator for the study, Dr. John Reckless of Bath, England, pushed to publish the unflattering findings on his own. Dr. Reckless’s office said Tuesday that he could not be reached for comment.

According to one September 2000 e-mail message by a Neurontin team leader at Pfizer, “The main investigator in the U.K. (Dr. Reckless) is keen to publish but this will have several ramifications.” The team leader later wrote, “I think we can limit the potential downside of the 224 study by delaying publication for as long as possible.”

Pfizer said Tuesday that it had submitted the Reckless study to two journals which declined to publish it. The results were not published until 2003 and, according to plaintiffs’ experts, when they did appear they were combined with two other studies and together the findings concluded Neurontin was effective for treating neuropathic pain.

Another series of e-mail messages had the subject line “Spinning Serpell,” a reference to an investigator on the study, Dr. Michael Serpell of Glasgow, Scotland. In the e-mail exchange a senior marketing manager for Pfizer and a professional medical writer discussed how to cast the results in a more favorable light for a poster presentation at a medical conference, the experts concluded.

“If Pfizer wants to use, present and publish this comparative data analysis in which two of the five studies compared make the overall picture look bad, how do we make it sound better than it looks on the graphs?” the medical writer asked.

Pfizer discontinued its marketing program for Neurontin in 2004 after the drug became available as a generic. That same year, the company paid $430 million to settle federal criminal and civil claims that Warner-Lambert, which Pfizer acquired in 2000, promoted Neurontin for unapproved uses during the 1990s.

At the time, Pfizer said the illegal marketing had occurred before Pfizer acquired the company or drug. On Tuesday, Pfizer repeated that it had instituted procedures when it acquired Warner-Lambert to make sure there was no off-label promotion of Neurontin.

Despite that settlement, separate legal action involving the drug is still pending in Boston, where consumers and third-party payers including insurance companies and trade unions want Pfizer to repay them billions of dollars for Neurontin prescriptions. The plaintiffs accuse Pfizer of fraudulently misrepresenting the drug’s benefits.

Thomas Greene, a lawyer for the plaintiffs, said the documents in the case revealed that even after the Neurontin settlement.

“Pfizer continued with the medical marketing firms and planted marketing messages in journal articles that Neurontin was effective while they knew that their own clinical trials had failed to demonstrate it was effective,” Mr. Greene said.

Dr. Dickersin, the Johns Hopkins expert, said that of 21 studies she reviewed, five were positive and 16 negative, meaning they did not prove the drug was effective. Of the five positive studies, four were published in full journal articles, yet only six of the negative studies were published and, of those, two were published in abbreviated form.