GSK Sales Reps told NOT to Divulge Paxil Data / Merck Withdraws Vioxx

GSK Sales Reps told NOT to Divulge Paxil Data / Merck Withdraws Vioxx

Thu, 30 Sep 2004

The Associated Press reports:
“Merck pulled Vioxx after admitting studies showed the drug raised the risk of heart attack. As recently as August, Merck “strongly” disagreed with studies showing the drug increased heart attack risk, and had recently gained FDA approval to market the drug to children.”
See: http://www.forbes.com/home/feeds/ap/2004/09/30/ap1569038.html

What, if any, safety standards does the FDA use when it approves a drug for marketing to children?

It is apparent that the FDA is infested with a disease that compromises the agency’s judgment about safety issue. The remedy can only be a thorough cleansing from the top down. FDA officials have consistently demonstrated that the financial interests of drug manufacturers take priority over children’s lives. FDA officials’ failure to exercise their authority to protect children from hazardous drugs should be cause for removal from office.

The manufacturers of antidepressants continue to market their drugs for children / adolescents even after a causal relation has been scientifically established between antidepressants, such as Paxil / Seroxat and suicide-related behavior. They do so because FDA officials continue to drag their feet about issuing black box warnings on antidepressant labels. Even after an FDA advisory panel urged the agency to require black box warnings about an increased suicide risk–on the labels read by physicians and on the package labels read by consumers–top officials are undecided.

The NJ Star Ledger obtained an internal (September 8, 2003) GlaxoSmithKline memo that was distributed to the company’s sales representatives. The memo advises them NOT to discuss the suicide-related risk of Paxil / Seroxat with doctors.

The subject of the memo: REVISED MEDICAL INFORMATION LETTER ON THE USE OF PAXIL IN PEDIATRIC PATIENTS

Since Paxil has not been approved for pediatric patients, and federal law prohibits GSK from marketing the drug off-label, what was the purpose of the memo? And what is the justification of failing to warn doctors about the life-threatening risk?

The 2003 memo cites a discredited published report in the Journal of the Academy of Child and Adolescent Psychiatry (2001, pp. 762-772) that maintained that Paxil was “safe and effective and well tolerated.” It was co-authored by leading US child psychiatrists.

However, its claimed findings are refuted by a 1998 internal GSK’s memo which states that only “positive data from study 329” would be published. The unpublished data, the memo stated, would not be published or submitted to the FDA because:

“It would be commercially unacceptable to include a statement that efficacy had not been demonstrated as this would undermine the profile of paroxetine [Paxil].”
See: http://www.ahrp.org/risks/SSRI0204/GSKpaxil/pg5.html

This 1998 memo served as NY State Attorney, Eliot Spitzer’s smoking gun in his suit against Glaxo. Even Dr. Thomas Laughren of the FDA noted that the published report incorrectly claimed positive findings. See:

The newly uncovered Sept. 2003 memo is strewn with misleading statements such as:
“There is no reliable or compelling evidence that Paxil causes suicide.”

Why were GSK sales reps provided with information about suicide data and admonished NOT to inform physicians?

Contact: Vera Hassner Sharav
Tel: 212-595-8974

Sales reps told not to divulge Paxil data
Drug maker memo cited risks to youth
Wednesday, September 29, 2004
BY ED SILVERMAN

Just as the safety of antidepressants became a controversy last year, one drug maker told its sales force not to talk to doctors about data linking its pill to serious side effects in children and adolescents.

In a memo last September, GlaxoSmithKline provided an update on concerns over its Paxil medicine, including study results showing a high incidence of suicide and hostility, but instructed its sales representatives in bold letters not to “discuss the contents” with doctors.

The memo, a copy of which was obtained by The Star-Ledger, comes to light after months of criticism of the pharmaceutical industry for allegedly withholding important clinical-trial data that cast antidepressants in a negative light.

Last month, Glaxo agreed to disclose trial data about its drugs to settle a lawsuit filed by the New York attorney general, who accused the company of fraud for concealing negative results about Paxil. Congress, meanwhile, is also investigating the allegations.

A Glaxo spokeswoman denied any attempt to conceal information from doctors. But ethics experts questioned the drug maker’s intentions.

“I’m confused about the motive and my first instinct is to be suspicious,” said Norman Fost, a pediatrics and medical ethics professor at the University of Wisconsin, and a member of a federal advisory panel that recently recommended severe warnings for antidepressants.

“It’s not transparent,” he said. “If the company sincerely wanted doctors to know about the risks of prescribing Paxil for children and adolescents, distributing the (clinical-trial) articles would have been the way to do that.”

Glaxo spokeswoman Mary Anne Rhyne said the sales reps were instructed not to speak with doctors about the clinical-trial results because drug companies are forbidden from engaging in any activity that may be considered off- label promotion.

“Our sales reps are prohibited from discussing, sharing or leaving behind off-label information with health care providers,” she said.

Off-label refers to promoting or prescribing a drug for a use not approved by the Food and Drug Administration. Among antidepressants, only Prozac has been approved for use in children and adolescents, although doctors are free to prescribe as they choose.

Another medical ethics expert said drug company sales reps should not promote off-label usage, but argued Glaxo had an obligation to inform doctors of negative trial data to protect patients.

“You don’t want to hide under the off-label excuse,” said Arthur Caplan of the Center for Bioethics at the University of Pennsylvania. “They do have a moral duty.”

Off-label prescriptions for those younger than 18 accounted for 8 percent of all antidepressant prescriptions during the first six months of this year, said Michael Evans of the FDA Office of Drug Safety, at an agency advisory meeting two weeks ago.

At that two-day session, the FDA advisory panel sat through presentations showing the drugs, as a group, are twice as likely as a placebo — or dummy pill — to cause suicidal thoughts or behavior in children. The drugs were also shown to be ineffective in children.

As a result, the panel recommended the FDA issue “Black Box” warnings, prominently placed on package inserts in hopes of quickly capturing the attention of doctors and patients. The FDA, which is also reviewing data on adults, may take action as early as this week.

In its September 2003 memo, U.K.-based Glaxo said pediatric trials involving Paxil did not find any patients who committed suicide. However, there has since been controversy over the way the company described such behavior, which prompted regulatory review of the data.

The memo included results from a study, known as 329, which concluded Paxil was safe and effective in youngsters. However, the study has since been questioned by critics, who note that 7.5 percent of patients suffered emotional liability, which refers to suicidal activity, versus 0 percent on placebo. Also, 6.5 percent experienced hostility versus 1 percent on placebo.

“This letter is for your informational purposes only,” the memo said. “Although you should read the letter carefully, please do not discuss the contents with your customers.”

The Glaxo spokeswoman said the study was published in the Journal of the American Academy of Child and Adolescent Psychiatry in July 2001 and was widely circulated.

David Fassler, a University of Vermont psychiatry professor and trustee of the American Psychiatric Association, said many child psychiatrists should have seen the article. But he also said the journal is “not necessarily read by many pediatricians and primary-care physicians.”

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