- Press Release
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- From today's issue of the American Psychiatric Association's
publication, Psychiatry News, in an article titled, "Congress Hammers
FDA Over Handling of SSRIs" we read:
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- "Unsatisfied with answers and explanations from
[FDA] agency officials during the second hearing, at least two committee
members, Rep. Diana DeGette (D-Colo.) and Rep. Bart Stupak (D-Mich.), threatened
to introduce legislation banning the prescribing of antidepressants to
anyone under age 18 "if the FDA didn't act forcefully and swiftly
to protect America's children."
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- Comments Vera Sharav of www.ahrp.org :
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- "How intreresting that this report in Psych Times,
an APA publication, more accurately reflects the two Cong hearings than
did any reports in the major ' independent' press! It is also disconcerting
that the press didn't grasp the significance of the ' missing' memos:
FDA officials like Knudsen, have 'off channel' discussions with drug manufacturers
that leave no trace in FDA's files. The Committee even announced that when
asked what the agency's document retention policy is, the FDA responded
"we have none!" Not a raised eybrow. "
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- Yet, the public and the press continue to act as if the
FDA exists to protect the public's interest! For decades the FDA has been
referred to as the Washington Branch for the phamaceutical giants. I commend
Congress for continuing to put pressure on the FDA to do what we have been
led to believe they are suppose to do - protect the public health.
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- And let me point out once again that there are TWO ongoing
Congressional investigations into these antidepressants and one Senate
investigation. With that in mind consider this:
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- -- It took only one Congressional investigation to have
LSD banned when Eli Lilly gave that drug to us as a cure for mental illness.
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- -- It took only one Congressional investigation to have
the benzodiazaphines [the Valium family of drugs] made controlled substances.
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- Clearly, with two Congressional investigations and one
Senate investigation into one group of drugs, this is one of the most important
public health issues facing this country today.
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- Ann Blake Tracy, Ph.D., Executive Director, International
Coalition For Drug Awareness Author: Prozac: Panacea or Pandora? - Our
Serotonin Nightmare & audio tape on safe withdrawal: "Help! I
Can't Get Off My Antidepressant!"
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- Order Number: 800-280-0730 Website: www.drugawareness.org
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- Congress Hammers FDA Over Handling Of SSRIs
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- Psychiatric News October 15, 2004 Volume 39 Number 20
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- By Jim Rosack
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- At press time, APA was waiting to hear whether the FDA
would issue a black-box warning for pediatric use of SSRIs. Here is a summary
of the events leading up to this strongly expected outcome.
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- Officials of the U.S. Food and Drug Administration (FDA)
first suspected an increase in suicidal thoughts and behaviors linked to
antidepressant use in children and adolescents in March 1996-eight and
a half years ago. Yet no apparent action was taken by the agency until
a pattern seemed to emerge in the first half of 2003.
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- During a dramatic pair of hearings before the House Energy
and Commerce Committee's Subcommittee on Investigations and Oversight last
month, FDA officials were repeatedly put on the defensive as to whether
there existed a conspiracy to cover up the link between the drugs and harmful
behaviors.
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- Unsatisfied with answers and explanations from agency
officials during the second hearing, at least two committee members, Rep.
Diana DeGette (D-Colo.) and Rep. Bart Stupak (D-Mich.), threatened to introduce
legislation banning the prescribing of antidepressants to anyone under
age 18 "if the FDA didn't act forcefully and swiftly to protect America's
children."
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- Committee members' frustration and anger seemed to have
built steadily through the first of the two hearings, which were held two
weeks apart. During the first hearing, on September 9, pharmaceutical company
executives were grilled about their apparent selective disclosure and publication
of clinical trial findings. Only four of the 15 trials of antidepressants
in pediatric patients with depression have been published-all with favorable
results.
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- Company executives fiercely defended their disclosure
records, noting that the vast majority of clinical trial data not published
in peer-reviewed journals-including negative data-had been presented on
more than one occasion as poster presentations or symposia during major
psychiatric meetings.
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- APA's Committee on Public Affairs was among the many
components that met last month in Washington, D.C., to conduct the Association's
work. More on the meetings appears on page 18 and page 19. Above are, from
left, Deborah Cross, M.D., Leslie Hartley Gise, M.D., and Britt Peterson,
M.D.
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- However, it was FDA Acting Deputy Commissioner for Operations
Janet Woodcock, M.D., who took the heat from committee members. They charged
that the FDA had shirked its responsibility to protect the public health
by not keeping track of all the data available and ensuring disclosure.
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- Woodcock reminded the committee members that the FDA
has little statutory authority to compel disclosure or publication, fueling
calls for a legislated mandatory clinical trials registry (see page 2).
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- During the second of the two hearings, held September
23, Rep. Joe Barton (R-Tex.), chair of the Energy and Commerce Committee,
emphasized Congress's frustration with the agency. "The fact that
children taking antidepressants were experiencing psychiatric adverse events
at greater rates than adults was known at the agency as far back as 1996
and 1997," Barton said. "I want to know what did the agency do
to respond to those concerns?"
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- Barton was referring to a previously undisclosed letter
from an FDA reviewer dated March 19, 1996, in reference to Pfizer's data
on the use of Zoloft (sertraline) in children and adolescents with obsessive-compulsive
disorder. The FDA letter said in part, "We note that there appears
to be an increased occurrence of suicidality events in pediatric patients
exposed to sertraline in pediatric trials" compared with observed
rates in comparable adult patients. In fact, there was a fivefold higher
risk in patients taking sertraline compared with those taking placebo.
The FDA medical reviewer asked Pfizer for "clarification and explanation"
of the data.
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- The subcommittee obtained the FDA's letter to Pfizer
from the company, not from the agency. FDA officials acknowledged that
no record of the memo was found in the agency's files. On March 28, 1996,
only a week after the letter asking for clarification and explanation,
the FDA approved Pfizer's application for pediatric exclusivity without
any apparent resolution of the medical reviewer's questions.
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- After the application had been approved, Pfizer responded
to the agency's request. That response was retained in the FDA's files.
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- Details also emerged about the agency's handling of a
report by FDA medical reviewer Andrew Mosholder, M.D., who had analyzed
the pediatric exclusivity data on antidepressants, submitted to the FDA
as required under the Best Pharmaceuticals for Children Act. Mosholder's
report was the first to assert openly an increased risk of suicidal thoughts
and behaviors associated with antidepressant use in children and adolescents.
While his analysis was instrumental in prompting an advisory committee
hearing in February, Mosholder was prevented from delivering his report
at that meeting.
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- Several members of Congress, including Barton, asked
numerous questions regarding the handling of Mosholder's report and why
he had not been allowed to deliver it at the public advisory committee
meeting.
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- Mosholder testified that after he had completed his report,
his superiors at the FDA did not agree with some of his conclusions and
recommendations-he had not only identified an association, but also recommended
actions that should be taken regarding strong warnings for the drugs. He
testified that there was "considerable discussion" at the agency
regarding the report and his interpretation of the SSRI pediatric exclusivity
data.
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- Robert Temple, M.D., the FDA's associate director for
medical policy, strongly defended the agency's handling of Mosholder's
report. "We were concerned about an overemphasis that could lead to
a deterrent to treatment," Temple testified. "At the same time,
we didn't want to ignore an important signal."
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- Members of Congress on the oversight committee pushed
Temple to explain why the agency waited so long to issue stronger warnings
on SSRI use in children, when the agency had Mosholder's report since mid
2003.
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- "We had questions that were not answered to our
satisfaction," Temple said. "We were not worried about [Mosholder's]
analysis of the data, but we had significant questions about the credibility
of the data he had available to analyze. We decided to withhold any agency
opinion on the issue till everything possible was known."
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- The FDA then decided to seek the independent reanalysis
of the data by suicidality experts at Columbia University, Temple said.
"We had no way of knowing what the reanalysis would bring-whether
it would strengthen or weaken [Mosholder's] conclusions. We really had
no preconceived notions, no preference."
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- Meanwhile, by late spring both House and Senate committees
began investigating the FDA's handling of the issue. Members of Congress
began expressing a sense of frustration over what they characterized as
"a slow and obstructive response."
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- "The FDA's lack of cooperation with the committee
in obtaining relevant and responsive information in a timely fashion on
a matter that involves the safety of our children leaves me wondering whether
this is sheer ineptitude or something far worse," Barton noted during
the first of the two hearings in September.
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- During the second hearing, it was revealed in documents
released by the committee that on at least one occasion, documented in
internal FDA e-mails between Mosholder and his superiors, Mosholder was
advised to change his conclusions, deleting material on the risks. An FDA
attorney then advised him to conceal the change when asked to submit documents
to Congress.
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- "I don't think it's necessary to indicate this document
represents a version of the earlier one by noting that things have been
omitted; that simply invites the committee to ask further questions about
what was omitted," wrote Donna Katz of the FDA's Office of Chief Counsel
in an e-mail to Mosholder.
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- The Columbia analysis, which took roughly four months,
was reviewed by an internal FDA Office of Drug Safety medical officer,
Tarek Hammad, M.D. Hammad's conclusions mirrored those of Mosholder: there
is roughly a one-and-a-half to twofold higher risk of suicidal thoughts
and behaviors in children and adolescents taking certain antidepressants.
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- "We had to proceed cautiously on such an important
matter," Temple emphasized. "To get it wrong would create more
problems than we could hope to solve."
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- The Columbia analysis, he added, helped to determine
that the data that Mosholder had analyzed were valid and, therefore, that
his conclusions were valid.
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- Following the second advisory committee hearings, on
September 13 and 14, several members of the subcommittee pressed Temple
to disclose what the FDA's final position would be (see article at right).
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- "Stating that the drugs are associated with, linked
to, or cause suicidal thoughts and behaviors in pediatric use is a given,"
Temple said. "What is at question is what form that warning will take.
It could be a black box; it could be a bolded warning within the warnings
section of the full label."
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- Stupak shot back, "When are you finally going to
decide?"
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- Temple replied that a decision would be made "within
a few days."
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- "But if these drugs don't work well in kids, and
they increase suicidality in kids, why does the FDA allow them to be prescribed
to kids?" Stupak asked. "Can't the FDA ban prescribing them to
children?"
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- "We could contraindicate their use," Temple
replied, "but we don't think that would be particularly helpful in
protecting the public health."
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- Temple emphasized more than once during his testimony
that the agency, as well as members of the advisory committees, had been
reluctant to contraindicate antidepressant use in children out of fear
that children who need care would not get it.
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- "Two-thirds of the [members of the committees] voted
in favor of a black-box warning," Temple emphasized, adding that when
a committee vote is split, the agency does not automatically go with the
majority-it must deliberate the pros and cons of each position and determine
the best course to take.
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- "There's no question there will be a strong warning,"
Temple said. "We need a patient med guide, and the drugs need to be
in unit dose packaging." That way, he explained, the warning language
required in labeling would be assured of getting to each patient taking
the medications at issue.
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- "The only thing we are still thinking about is the
box," Temple concluded. "All the rest of the advisory committee's
recommendations will be implemented."
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- http://pn.psychiatryonline.org/cgi/content/short/39/20/1
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