[News] Experts Conclude Pfizer Manipulated Neurontin Studies

[Birdbomb]

Experts Conclude Pfizer Manipulated Studies

Source

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 Vioxx, a painkiller, was withdrawn from the market in 2004 after research indicated it could cause strokes and heart attacks.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.

[hawke86]

Thanks for the information. It was helpful.

[BuckeyeFan]

All for the same core reason behind the market collapse. Constant pressure to show a profit each and every week, month, quarter, and year. No one is in it for the long run anymore. They have to make the big bucks right now.

[Meetz1064]

can say is how very very sad. "Tis pure GREED and nothing but.

[Cint]

Before it was bought by Pfizer, Warner-Lambert promoted Neurontin and it's unapproved uses during the 1990s through some of the well known neurologists in America. Here is another article:

Real Drug-related Criminal Behavior
Neurontin Usage Is Finally Looked Into
- Promoting An Inappropriate Drug?

Court Papers Suggests Scale of Drug's Use
New York Times - May 30, 2003- by Melody Petersen

Warner-Lambert paid dozens of doctors tens of thousands of dollars each to speak to other physicians about how Neurontin, an epilepsy
drug, could be prescribed for more than a dozen other medical uses that had not been approved by the Food and Drug Administration.

The top speaker for Neurontin, Dr. B. J. Wilder, a former professor of neurology at the University of Florida, received more than $300,000 for speeches given from 1994 to 1997, according to a court filing. Six o! ther doctors, including some from top medical schools, received more than $100,000 each.

Other doctors were paid to write reports on how Neurontin worked for a handful of their patients, the court papers said. Still others were
paid to prescribe Neurontin in doses far exceeding the approved levels as part of a clinical trial that Warner-Lambert created to market the medicine, according to the court papers, which are new
documents filed in the lawsuit by the whistle-blower. The papers are backed up by hundreds of pages of corporate documents and memos
recently filed with the court.

It is illegal for a drug company to market a medicine for uses the F.D.A. has not approved, but doctors can prescribe a drug in any manner that they think is best for their patients.

Lawyers for Dr. Franklin argued that the company relied on the doctors to market Neurontin for unapproved uses because it was illegal for the
company to do so. The speaking program, which also included paying doctors to listen to the speeches at hotels and resorts, was called peer selling, according to the documents.

Also this week, prosecutors filed a brief supporting Dr. Franklin. The United States attorney in Boston, Michael J. Sullivan, asserted in the brief that his lawyers had "presented evidence of an illegal off-label marketing scheme that is rife with false statements and fraudulent conduct."

For example, Mr. Sullivan said, Warner-Lambert had invited doctors to continuing medical education classes that the company said would provide unbiased information about Neurontin. In fact, Mr. Sullivan said, some of these classes were "a massive promotion" in how Neurontin could be used to relieve pain and were planned by Warner-Lambert employees.

Mr. Sullivan's brief, filed on Tuesday, was significant. Even though prosecutors have said in court that they are conducting both a civil
and a criminal investigation into the accusations, the federal government has not formally entered the case as a plaintiff. Mr. Sullivan filed the brief after Pfizer, which acquired Warner-Lambert
in 2000, asked the court to throw out the case, arguing that Dr. Franklin had not proved that the company violated the law.

Corporate documents made public in the case yesterday state that a Warner-Lambert strategy was to focus on respected doctors in the major teaching hospitals who would serve as "Neurontin champions."

One of those was Dr. Steven C. Schachter, a professor at Harvard Medical School and a physician at Beth Israel Deaconess Medical Center in Boston. Dr. Schachter received $71,477 from May 1994 to
September 1997 to speak about Neurontin to other doctors, according to the court papers.

At a meeting Warner-Lambert sponsored for physicians at the Ritz-Carlton Hotel in Boston in 1996, Dr. Schachter said that "pain specialists are finding that low dosages of Neurontin are effective" — a statement that lawyers for Dr. Franklin called misleading. Paul Cirel, a lawyer for Dr. Schachter, declined yesterday to comment.

! Another doctor, Ilo Leppik, a professor at the University of Minnesota, received $49,250 to speak about Neurontin. According to the court papers, Warner-Lambert also paid $303,764 to publish Dr.
Leppik's textbook on epilepsy.

Dr. Leppik said yesterday that in his speeches he had talked only about how Neurontin could be used in epilepsy. He said his textbook mentioned not just Neurontin, but also all other epilepsy medicines.

"I'm an academic," Dr. Leppik said. "I'm not a marketer. I'm proud of that book. I don't think of it as a marketing vehicle at all."

Dr. Wilder, who received the most money for speaking about Neurontin, could not be reached yesterday. His wife, Eve Wilder, said that
Warner-Lambert had never told her husband what to say. "He had total freedom on all the education programs he put on," Mrs. Wilder said.

Warner-Lambert tracked doctors' prescriptions to see if the numbers increased after the ! doctors attended Neurontin meetings or after they
were hired to spe ak about the drug. For example, Dr. Joseph De Mayo, a Connecticut physician, wrote 58 prescriptions for Neurontin for unapproved uses like gastric ulcer, osteoarthritis and backache in the 14 months after he attended a meeting at the Ritz-Carlton in Atlanta where other doctors had spoken about Neurontin, according to court documents.
In the year before that meeting, Dr. De Mayo did not write any Neurontin prescriptions for Medicaid patients, the papers said.

After the meeting, Dr. De Mayo also became a Warner-Lambert speaker and was paid more than $1,000, according to the papers. Dr. De Mayo
said yesterday he had not seen the lawsuit and could not comment.

In 2000, 88 percent of Neurontin sales were for uses not approved by the F.D.A., according to the lawsuit. Until last year, Neurontin was approved only for use in epilepsy as an add-on medicine when the patient's primary drug did not work. Last year, the F.D.A. approved Neurontin for use in pain suffered by patients with shingles.
Dr. Franklin has said that Warner-Lambert also told its sales representatives to promote Neurontin to doctors for unapproved uses. Until now, that accusation has largely rested on the testimony of the whistle-blower, who visited doctors as a Warner-Lambert medical liaison. The newly filed court papers, however, give details from Scott-Levin, a health industry consulting firm in Newtown, Pa., that Warner-Lambert hired to track what its sales representatives were saying to doctors.

According to computer records from Scott-Levin, almost half of the 503 doctors surveyed from October 1995 to December 1998 said they had
received marketing appeals from the company's sales representatives on unapproved uses. And of those doctors, about half told Scott-Levin that they intended to increase their prescribing of Neurontin, the court documents say.

Copyright 2003 The New York Times Company
[/I]

[Birdbomb]

Know what's so sickening about this, even though Pfizer took responsibility, they made a butt-load of money off this drug and only paid out a token fine.

In my book, any doctor whom lowers his standards to sell for big pharma is no better than the lowly junkie selling illegal dope on the streets. He's just doing it in a better neighborhood


What's real scary, medical implant companies have followed suit.

[Dutch mom]

http://www.nytimes.com/2007/11/25/ma...in&oref=slogin

By Dr. Daniel Carlat (assistant clinical professor of psychiatry at Tufts University School of Medicine and the publisher of The Carlat Psychiatry Report), 'Dr. Drug Rep', New York Times Magazine, November 25, 2007:

Was I swallowing the message whole? Certainly not. I knew that this was hardly impartial medical education, and that we were being fed a marketing line. But when you are treated like the anointed, wined and dined in Manhattan and placed among the leaders of the field, you inevitably put some of your critical faculties on hold.

How many doctors speak for drug companies? We don’t know for sure, but one recent study indicates that at least 25 percent of all doctors in the United States receive drug money for lecturing to physicians or for helping to market drugs in other ways. This meant that I was about to join some 200,000 American physicians who are being paid by companies to promote their drugs. I felt quite flattered to have been recruited, and I assumed that the rep had picked me because of some special personal or professional quality.

Naïve as I was, I found myself astonished at the level of detail that drug companies were able to acquire about doctors’ prescribing habits. I asked my reps about it; they told me that they received printouts tracking local doctors' prescriptions every week. The process is called “prescription data-mining,” in which specialized pharmacy-information companies (like IMS Health and Verispan) buy prescription data from local pharmacies, repackage it, then sell it to pharmaceutical companies. This information is then passed on to the drug reps, who use it to tailor their drug-detailing strategies. This may include deciding which physicians to aim for, as my Wyeth reps did, but it can help sales in other ways.

Driving home, I went back over the talk in my mind. I knew I had not lied — I had reported the data exactly as they were reported in the paper. But still, I had spun the results of the study in the most positive way possible, and I had not talked about the limitations of the data. I had not, for example, mentioned that if you focused specifically on patients taking between 200 and 300 milligrams per day, a commonly prescribed dosage range, you found a 3.7 percent incidence of hypertension. While this was not a statistically significant higher rate than the placebo, it still hinted that such moderate doses could, indeed, cause hypertension. Nor had I mentioned the fact that since the data were derived from placebo-controlled clinical trials, the patients were probably not representative of the patients seen in most real practices. Patients who are very old or who have significant medical problems are excluded from such studies. But real-world patients may well be at higher risk to develop hypertension on Effexor.
I realized that in my canned talks, I was blithely minimizing the hypertension risks, conveniently overlooking the fact that hypertension is a dangerous condition and not one to be trifled with. Why, I began to wonder, would anyone prescribe an antidepressant that could cause hypertension when there were many other alternatives? And why wasn’t I asking this obvious question out loud during my talks?

A year after starting my educational talks for drug companies (I had also given two talks for Forest Pharmaceuticals, pushing the antidepressant Lexapro), I quit. I had made about $30,000 in supplemental income from these talks, a significant addition to the $140,000 or so I made from my private practice.

[Birdbomb]

Top Psychiatrist Didn’t Report Drug Makers’ Pay

One of the nation’s most influential psychiatrists earned more than $2.8 million in consulting arrangements with drug makers from 2000 to 2007, failed to report at least $1.2 million of that income to his university and violated federal research rules, according to documents provided to Congressional investigators.

The psychiatrist, Dr. Charles B. Nemeroff of Emory University, is the most prominent figure to date in a series of disclosures that is shaking the world of academic medicine and seems likely to force broad changes in the relationships between doctors and drug makers.

In one telling example, Dr. Nemeroff signed a letter dated July 15, 2004, promising Emory administrators that he would earn less than $10,000 a year from GlaxoSmithKline to comply with federal rules. But on that day, he was at the Four Seasons Resort in Jackson Hole, Wyo., earning $3,000 of what would become $170,000 in income that year from that company — 17 times the figure he had agreed on.

The Congressional inquiry, led by Senator Charles E. Grassley, Republican of Iowa, is systematically asking some of the nation’s leading researchers to provide their conflict-of-interest disclosures, and Mr. Grassley is comparing those documents with records of actual payments from drug companies. The records often conflict, sometimes starkly.

“After questioning about 20 doctors and research institutions, it looks like problems with transparency are everywhere,” Mr. Grassley said. “The current system for tracking financial relationships isn’t working.”

The findings suggest that universities are all but incapable of policing their faculty’s conflicts of interest. Almost every major medical school and medical society is now reassessing its relationships with drug and device makers.......click here for the rest of the article

Senator Grassley is the MAN!

[Meetz1064]

there's SOMEONE out there who's REALLY HONEST!!! That means there is HOPE!!! YEAHHHH!!!

[Cint]

for Senator Grassley!!

Let's just hope that Sen. Grassley & group can get to the bottom of the pharmaceutical scoundrels' (like Dr. Nemeroff) lies and deception.

[RobinN]

Research into internal company documents has revealed that Pfizer Inc., the world's largest research-based pharmaceutical company, tampered with the results of at least 16 study reports about its epilepsy drug, Neurontin. In order to expand the market for the drug, Pfizer unlawfully removed, altered, and changed published study findings that revealed unfavorable results.

Of the 20 study reports that were produced, eight of them were not published in medical journals at all and another eight had their original study designs altered in some way in order to arrive at alternate outcomes. Some of the primary outcomes were changed to new ones while others were replaced by secondary outcomes. Still others were simply removed altogether

http://www.naturalnews.com/027692_sc...Neurontin.html

http://abcnews.go.com/Health/wiresto...9057680&page=2

[Meetz1064]

just doesn't surprise me, as sad as that is......

[Bernard]

Apparently, there was insufficient evidence that Pfizer's malfeasance was responsible for damages to some insurance carriers who paid for off label uses of Neurontin:

Pfizer Inc., the world’s largest drugmaker, won dismissal of fraud claims by Aetna Inc. and Guardian Life Insurance Co. in a lawsuit over its marketing of the epilepsy drug Neurontin.

U.S. District Judge Patti Saris in Boston yesterday dismissed Aetna’s and Guardian’s claims that they were forced to overpay for Neurontin prescriptions because Pfizer misled them into believing the drug was effective for “off-label” uses. Saris declined to throw out similar claims against Pfizer by Kaiser Foundation Health Plan Inc.

Saris ruled that Aetna and Guardian failed to present sufficient evidence that they were directly harmed by claims made by Pfizer or Warner-Lambert Co., which was acquired by Pfizer in 2000, about the effectiveness of Neurontin for conditions other than epilepsy, for which the drug has been approved by the U.S. Food and Drug Administration.

“There is no evidence in the record that Guardian or Aetna at any point directly relied on Pfizer’s ‘half truths,’ communicated through its alleged manipulation and withholding of studies that suggested Neurontin’s ineffectiveness for off-label indications,” Saris wrote.

Kaiser, which Saris called “a more hands-on third party payor,” showed that it had considered Pfizer’s allegedly false claims and data in deciding to pay for Neurontin prescribed for illnesses other than epilepsy.
...

http://www.bloomberg.com/apps/news?p...d=a56.g5.bnhVg

Kaiser's claim/suit is still pending.

[epileric]

A lawsuit over the anti-seizure drug Neurontin began in the United States on Monday, with patients, insurance companies and unions accusing the drug manufacturer of aggressively marketing it as pain medication, an unapproved use.

http://www.cbc.ca/world/story/2010/0...n-lawsuit.html