Glaxo Attracts Questions
Over Data in Paxil Studies
Claims Suicide Risk
By ALICIA MUNDY and JEANNE WHALEN
June 14, 2008; Page A4
WASHINGTON -- GlaxoSmithKline PLC faces new
questions about whether it deliberately misrepresented data on suicide
risk for its antidepressant Paxil when it applied for the drug's
approval to the U.S. Food and Drug Administration at an advisory
committee meeting in 1991, a charge the company has denied.
A study by a Harvard psychiatry instructor,
underwritten by plaintiffs' lawyers and previously kept under seal by a
court order, says that Glaxo "improperly" counted patients taking
placebos during clinical studies. From 1989 through 1991, Glaxo then
submitted information to the FDA that indicated no major difference in
risk of suicidal behavior, or suicidality, as doctors call it, between
patients who took Paxil and those who took a placebo.
However, Glaxo's counting minimized the differences
between suicidality rates in the Paxil and placebo groups, according to
the report. For instance, the company counted placebo patients who had
attempted or committed suicide before the study formally started, which
enhanced the results for Paxil.
The real risk for suicidality from Paxil, says the
report's author, Joseph Glenmullen, was eight times its risk for
patients on placebo. "Glaxo was aware of this risk, and hid it," Dr.
Glenmullen's report states. The drug was approved for sale in the U.S.
in 1992. Dr. Glenmullen said, in an interview Thursday, that if Glaxo
had given the agency the "correct" data in 1991, the FDA would likely
have added warnings about the risk for suicidality when it approved
In 2004, the FDA called for added warnings on popular
antidepressants known as selective serotonin-reuptake inhibitors, or
SSRIs, about potential links to suicidal behavior. In 2006, Glaxo sent
a letter to doctors stating that its studies showed that the risk of
suicidality in depressed adults was 6.7 times as high in patients
taking Paxil as in those taking a placebo.
Thursday, Sen. Chuck Grassley, an Iowa Republican,
released Dr. Glenmullen's study and a letter to the FDA, asking it to
investigate the original approval process for Paxil and Glaxo's
application in light of Dr. Glenmullen's report.
A Glaxo spokeswoman emailed a company statement that
was originally issued Feb. 6, when an earlier version of Dr.
Glenmullen's report was first unsealed by a court. That version was
missing nine pages that included information on Glaxo's counting
"GlaxoSmithKline has provided the U.S. Food and Drug
Administration over the years with numerous reports from its clinical
studies," the statement says. "As soon as GlaxoSmithKline became aware
of a potential increased risk in certain populations, it proactively
brought it to the attention of FDA and other regulatory bodies."
The statement notes that Dr. Glenmullen was hired by plaintiffs' lawyers, and calls his report "unscientific and misleading."
Sen. Grassley also raised concerns about a British
investigation that concluded this year that Glaxo should have alerted
British regulators earlier than it did about a link between Paxil and
suicidal behavior. He said evidence in the two reports raises questions
about whether the company kept U.S., as well as British health
officials, in the dark.
In March, British authorities concluded a four-year
investigation on whether Glaxo failed to inform the U.K. drug regulator
in a timely manner about a link between Paxil and suicidality in
children and teens. They said they saw no basis for criminal
prosecution of Glaxo because U.K. laws were unclear about whether
companies were obligated to report certain drug data. But the regulator
said it remained "concerned that GSK could and should have reported
this information earlier than they did."
Glaxo at the time said: "We firmly believe we acted properly and responsibly."
Paxil was made by SmithKline Beecham, which merged
with Glaxo Wellcome in 2000. SmithKline's former top executive,
Jean-Pierre Garnier, who was Glaxo's CEO until last month, said in a
2006 deposition in a lawsuit that the original data given to the FDA
shouldn't have included some of the placebo patients. In another 2006
court document, Glaxo "admits that five of six 'attempted suicide'
events" in the placebo group took place before the studies began.
During the 1991 meeting, members of the FDA's advisory
committee repeatedly said they wished there were more data to review on
suicidality, but, the report said, "unbeknownst to the committee, the
data already existed."
Write to Alicia Mundy at firstname.lastname@example.org and Jeanne Whalen at email@example.com