The Washington Post
Friday, September 24, 2004; Page A08
FDA Told Its Analyst to Censor Data on Antidepressants
By Shankar Vedantam
Washington Post Staff Writer
A Food and Drug Administration medical officer was told by top agency
officials to delete material on the risks of antidepressant drugs from
records he was submitting to Congress and then to conceal the deletions,
according to documents released yesterday at a hearing on Capitol Hill.
A bipartisan House panel said the FDA also repeatedly prevented Andrew D.
Mosholder from disclosing his conclusions that the medications increase the
risk of suicidal thoughts and behavior among children, potentially delaying
the issuance of a public warning. During the day-long hearing, legislators
repeatedly accused the agency of obfuscating the risks, slowing action and
subjecting Mosholder to harassment.
The disclosures added a new dimension to a year-old controversy over the use
of antidepressant drugs in children, which led a government advisory panel
to recommend last week that the FDA require a strongly worded "black box"
warning on the medications. While depression itself is known to increase the
risk of suicidal behavior, two FDA analyses, including one by Mosholder,
have concluded that the drugs may double the risk of suicide among some
children.
After revelations that Mosholder was asked not to present his findings at a
public forum in February led to an outcry, the agency's internal
investigative arm told Mosholder he might be subject to disciplinary action,
the documents showed. He was asked whether he had leaked his findings to the
news media and denied doing so.
He then prepared a sworn statement about his findings and stated that he had
been targeted by the internal inquiry. When investigators working for Senate
Finance Committee Chairman Charles E. Grassley (R-Iowa) sought a copy of his
records, Donna Katz of the FDA's Office of Chief Counsel urged him to delete
material from the statement and submit a cleaned-up version.
"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," Katz
wrote in an e-mail to Mosholder on May 4.
Among Katz's suggested edits was a section where Mosholder stated: "I
understand this statement is part of the Office of Internal Affairs
investigation and have been informed that I may be subject to disciplinary
proceedings."
Investigators from Grassley's committee, as well as the House Energy and
Commerce subcommittee on oversight and investigations, which conducted
yesterday's hearing, have said they were outraged to learn that Mosholder
had been the subject of an internal inquiry and disciplinary threats.
Mosholder declined to make the changes Katz requested, saying they would be
tantamount to perjury. He asked instead to black out the material, which
would have let congressional investigators know there had been deletions.
The FDA said the deletions were required because agency rules require that
ongoing investigations be kept secret.
The hearing produced new demands from legislators to know why the FDA did
not respond sooner to concerns about the widely used antidepressants.
Mosholder said he found as early as last September that drugs such as Paxil,
Zoloft and Effexor were associated with an increased risk of suicide among
children.
Agency officials praised his work but did not act on it, citing a lack of
confidence in the data. Even after British regulators warned doctors not to
prescribe most antidepressants to children last December, the FDA declined
to make Mosholder's findings public. Instead, they had the data reanalyzed
by Columbia University scientists. That evaluation resulted in a report last
month largely identical to Mosholder's findings a year ago.
"Was the public health served by a longer deliberative process in this
case?" asked Rep. Greg Walden (R-Ore.).
Robert J. Temple, the FDA's associate director for medical policy, defended
the agency's cautious approach. He said regulators are days from issuing new
warnings about the drugs and perhaps "a couple of weeks" from "probably"
acting on the recommendation that the labels carry a prominent warning.
Regulators are weighing whether to add to the labels information about
studies that found most of the drugs to be no more effective than sugar
pills.
Another document released yesterday showed that as far back as 1996, an FDA
official had suggested an increased risk of suicide among children taking
Zoloft. Rep. Joe Barton (R-Tex.) asked why the finding had not been followed
up.
"When did the FDA first become aware of a potential link between
antidepressants and suicidality in children, and what did they do to get to
the bottom of it?" asked Barton, who chaired the hearing.
FDA officials acknowledged that a letter sent at the time to Zoloft's
manufacturer, Pfizer Inc., is no longer in the agency's files.
Agency officials repeatedly said that they were worried that the controversy
would needlessly frighten parents and families away from useful drugs. Many
clinicians believe the drugs are effective against depression.
Link here
Los Angeles Times
September 24, 2004
Lawmakers Take FDA to Task on Antidepressants
A House subcommittee says the agency held back data on the drugs' risks to
children.
By Elizabeth Shogren,
Times Staff Writer
WASHINGTON - Members of Congress on Thursday accused the Food and Drug
Administration of suppressing information, for as long as eight years, about
the increased risks of suicidal thought and behavior in children and
teenagers taking antidepressants.
"There is something terribly rotten at the FDA," said Rep. Peter Deutsch
(D-Fla.). "No agency charged with protecting public health should have
behaved with such indifference."
During a House subcommittee hearing on the FDA review of clinical trials
involving the widely prescribed drugs, the legislators also criticized FDA
officials for withholding information from clinical trials about the lack of
benefit for children from most antidepressants.
"The FDA knew about the lack of efficacy in these clinical trials several
years ago, and nothing has been done to change labels to inform doctors,
patients and parents," said Rep. Greg Walden (R-Ore.), chairman of the
hearing of the House Energy and Commerce oversight and investigations
subcommittee.
FDA officials defended their decisions to keep data gathered in clinical
trials from the public.
"The higher-ups felt the data weren't ripe for presentation," said Dr.
Robert Temple, a director at the FDA's center for drug evaluation and
research.
Temple said agency officials were worried about scaring young patients away
from the drugs.
"Having untreated depression is risky too," he said.
About 1,600 teens - many of them suffering from depression - commit suicide
each year, according to the FDA.
The FDA is under intense congressional scrutiny for its failure to move more
quickly to warn doctors and parents about the increased risk of suicidal
behavior in children on antidepressants. Two FDA advisory committees
recommended last week that the agency order drug companies to place
prominent warnings on drug packaging and on the prescribing information that
goes to physicians.
"We don't want children taking an antidepressant drug if there appears to be
quite a bit of evidence that not only does it not help them, but in some
cases it actually hurts them by increasing the risks" of suicidal thought,
said Rep. Joe Barton (R-Texas), chairman of the Energy and Commerce
Committee.
Doctors last year wrote about 15 million prescriptions of nine
antidepressants for children and teens, according to an analysis from the
FDA and from IMS Health, a pharmaceutical information and consulting
company.
Fluoxetine hydrochloride, marketed by Eli Lilly & Co. as Prozac, is the only
antidepressant approved by the FDA for use in children because it has met
the agency's standard of effectiveness in clinical trials. But because they
are not prohibited from doing so, physicians regularly prescribe other
similar drugs to young patients.
In Thursday's daylong hearing, legislators questioned a decision by senior
FDA officials to prevent an agency researcher, Dr. Andrew Mosholder, from
presenting his analysis of data from clinical trials of antidepressant use
by children to two FDA advisory committees in February. His report showed
that children taking the drugs were almost twice as likely to exhibit
serious suicide-related behavior as those taking placebos.
Mosholder presented his findings at last week's advisory committee meeting,
but only after news of his report had leaked to the media and a
reexamination of the data by a Columbia University team and another FDA
researcher had confirmed his conclusions.
Mosholder analyzed data on Prozac, Zoloft, Celexa, Effexor, Luvox, Paxil,
Remeron, Serzone, Wellbutrin and Lexapro. All but Lexapro were included in
the reexamination of the clinical trials.
The legislators also grilled FDA officials about documents from as early as
1996 that suggested a possible connection between antidepressants and
suicidal tendencies in children.
In March 1996, Dr. James F. Knudsen, an FDA researcher, wrote to an
executive at Pfizer Inc. that "there appears to be an increased frequency of
reports of suicidality in the pediatric/adolescent patients exposed to" the
company's antidepressant, Zoloft, in clinical trials.
But Dr. Thomas Laughren, the FDA team leader who supervised Knudsen, told
the hearing that he analyzed the data referred to in the letter and
concluded that they did not "represent a signal of risk."
He said there was no reason the question of whether the drugs caused
suicidal tendencies in children should have been on the agency's "radar
screen" between 1996 and last year, when Mosholder's analysis revealed the
possible link.
But legislators on the panel were not convinced.
HEARING on
FDA's Role in Protecting the Public Health: Examining FDA's Review of Safety
& Efficacy Concerns in Anti-Depressant Use by Children
Subcommittee on Oversight and Investigations took place at
11:00 AM
September 23, 2004
at 2123 Rayburn House Office Building,
Washington, D.C.
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