Drug manufacturer GlaxoSmithKline PLC misled consumers and committed fraud by suppressing clinical studies that raised doubts about the safety and effectiveness of its top-selling antidepressant Paxil when used to treat children and adolescents, New York state Attorney General Eliot L. Spitzer alleged in a civil lawsuit filed Wednesday.
The complaint filed in New York state Supreme Court alleges that Glaxo systematically withheld negative information about the drug, also known as paroxetine. While the company's representatives and sales literature drew attention to a single study that showed Paxil had positive results, they hid four other studies, the complaint says. Unmentioned were studies that that found no clear evidence that the drug is effective in minors and that suggested it could increase the risk of suicidal thoughts and behavior.
The complaint cites a 1998 internal Glaxo memo that said the company's "target" was to "effectively manage the dissemination of these data in order to minimize any potential negative commercial impact."
The Food and Drug Administration has not approved Paxil for use by children, and Glaxo is not allowed to market the drug for minors. But doctors can prescribe Paxil for children as a "off-label" use. More than 2.1 million paroxetine prescriptions for children were written in 2002, the complaint says.
The complaint also alleges that Glaxo gave sales representatives copies of the positive study with a cover memo that said, "Paxil demonstrates REMARKABLE Efficacy and Safety in the treatment of adolescent depression."
GlaxoSmithKline said in a written statement that the firm "has acted responsibly in conducting clinical studies in pediatric patients and disseminating data from those studies. All pediatric studies have been made available to the FDA and regulatory agencies worldwide. We have publicly communicated data from all pediatric studies. As for the 1998 memo, it is inconsistent with the facts and does not reflect the company position."
The unpublished studies cited in the Spitzer lawsuit have been under discussion in the medical world for some time. British regulators cited them last year last year when they warned doctors against prescribing Paxil and several other popular antidepressants to children. The FDA recently urged doctors to watch patients carefully for suicidal behavior in the first weeks after prescribing antidepressants and ordered further study of possible connections between the drugs and suicide risk.
A separate study sponsored by the National Institute of Mental Health found that the antidepressant Prozac reduced the risk of suicide in teenagers, especially when combined with psychotherapy. Prozac is approved by both U.S. and British regulators for use in children.
In the case of Paxil, Spitzer is arguing that Glaxo's sales representatives had a duty to discuss the negative studies when promoting the drug.
"The manufacturer cannot rely exclusively on the positive study. . . . Where they affirmatively state this drug is 'remarkably' efficacious and safe, and they are withholding information that challenges that, that's wrong," Spitzer said in an interview.
Like previous investigations of biased research on Wall Street and trading abuses in the $7.5 trillion mutual fund industry, Spitzer's lawsuit uses New York law to take on an issue generally the province of federal regulators, particularly the FDA.
But Spitzer argued that "off label" uses, prescribed without FDA approval, are in a gray area and that he is just trying to make sure that doctors have the information they need.
"The last thing that I should be doing is making clinical decisions about which medicines are good or bad," Spitzer said. "We don't want to discourage off-label uses, we just want more complete information."
An FDA spokeswoman declined to comment on the lawsuit. Under federal law, when drug companies run studies of their drugs' effectiveness against new illnesses or in new population groups, they must submit the results to the FDA. But the data are considered proprietary commercial information and do not have to be disclosed publicly unless the FDA determines that important issues of safety are involved.
Some medical organizations and patients groups have become increasingly concerned that the drug companies are hiding information that doctors and patients need.
"A lot of these negative studies do get buried, and it's intentional. That's not a particular concern if it's a drug in the early stages [of testing] and hasn't been approved. But this is in use," said Wayne K. Goodman, a University of Florida psychiatry professor who sat on the FDA advisory committee that reviewed studies of antidepressants and adolescent suicide last winter.
Several medical groups and experts in adolescent psychiatry said they supported Spitzer's goals but did not know enough about New York law to comment on the lawsuit itself.
"Physicians, researchers and patients need and are entitled to as much information as possible to make decisions about treatment," said David G. Fassler, a Vermont psychiatrist who is on the council of the American Academy of Child and Adolescent Psychiatry. "The issue is significant and important. It doesn't just relate to psychiatry and antidepressants."
Outside legal experts said Spitzer appears to be on solid legal ground by bringing his case under the state's law against consumer fraud. States have a history of bringing legal actions against drug companies over pricing and marketing. Just last month a subsidiary of Pfizer Inc. paid $430 million to settle federal and state investigations into the way it promoted the drug Neurontin.
"It is not unusual for state attorneys general to be involved in pharmaceutical cases, and it is not unusual for them to bring cases against unfair and deceptive practices," said James E. Tierney, who heads Columbia Law School's National State Attorneys General Program. "This is a natural outgrowth."
Britain-based Glaxo's stock closed at $41.39, down $1.38, Wednesday on the New York Stock Exchange.