Fwd: [SSRI-Research] Expert FDA Report: SSRI Suicide risk-SF Chronicle / NYT/ NJ Ledgfer/ AP

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Sat, 17 Apr 2004 15:05:32 -0000

[sSRI-Research] Expert FDA Report: SSRI Suicide risk-SF Chronicle /

NYT/ NJ Ledgfer/ AP

 

 

Dianne Murphy MD (murphyd); Janet Woodcock MD ;

Lester Crawford (LCRAWFORD); Robert Temple MD

(temple); Russell Katz MD (katzr); Thomas

Laughren

(LAUGHREN)

Cc: Daniel Troy (dtroy)

 

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP) Promoting openness and

full disclosure http://www.ahrp.org <http://www.ahrp.org>

 

FYI

 

FDA officials have provoked congressional hearings at which they will

have to explain, not only why they concealed data linking

antidepressants to increased violent and suicidal behavior, and why

they covered up a report by the agency's primary medical expert, Dr.

Mosholder, confirming the risk. They will also have to explain why

they should be allowed to continue in their office inasmuch as the

information they deliberately concealed from physicians and parents

is critical to the life safety and health of our nation's children.

 

Congress is faced with an acute public health policy issue that pits

children's health and safety against Big Pharma and senior FDA

officials who were caught covering up unpublished evidence

demonstrating a two-fold suicidal risk for children taking an

antidepressant.

 

FDA's cover-up helped Big Pharma succeed in marketing these drugs

widely--to pediatricians, family physicians, child psychiatrists, and

directly to parents who were kept in the dark about the drugs'

potential life-threatening risks. As a result, nearly 11 million

antidepressant prescriptions were written for children in 2002-of

which 2.7 million were for children under 12. It is unfathomable why

preschool children in the US are the fastest growing market for

antidepressants! See: http://www.express-

scripts.com/other/news_views/outcomes_research.htm.

 

On Feb 1, 2004, The San Francisco Chronicle reported that FDA

officials were silencing Dr. Andrew Mosholder, the agency's own

expert medical officer, preventing him from reporting his analysis of

the unpublished data and his recommendations to the FDA advisory

committee at a public hearing (Feb 2, 2004).

 

Dr. Mosholder's report was released only at the insistence of 2

Congressional committees. His recommendation puts the lives of

children ahead of the drug industry's marketing goals. He

wrote: " Given the strength of the association shown by the present

data, the clinical importance of the apparent effect, and the fact

that the additional analyses are likely to take several more months

to complete while considerable numbers of pediatric patients are

being exposed to these drugs, I favor an interim risk management

plan. "

 

The New York Times reports " Recent studies have shown that children

given antidepressants are more likely to become suicidal than those

given placebos. But the studies have lead to different

interpretations by psychiatrists. The refusal by drug companies to

publish the studies has worsened the confusion. Internal agency

documents obtained by The New York Times show that federal health

officials are divided, too. "

 

What is left out is the underlying reason for the " different

interpretations by psychiatrists. " That is, the psychiatrists'

financial conflicts of interest which likely prompts them to defend

the drugs' value and safety. But given the absence of any scientific

evidence to back up their assertions about the drugs, these

assertions appear to reflect their bias toward the companies that pay

them.

 

For this reason AHRP questions the credibility of a data analysis by

investigators from the psychiatry department of Columbia University.

Inasmuch as they are among the staunchest public defenders of these

drugs, with very substantial financial ties to the drug

manufacturers, they are neither objective nor unbiased. Dr.

Mosholder, by contrast, is an impartial expert with no financial ties

to the drug manufacturers; his independent analysis is, therefore,

far more credible than theirs.

 

Dr. Mosholder's analysis and conclusions confirm the British

medicines authority and corroborate independent analyses of--not one,

not two, but a growing number of analyses by expert international

clinical trialists and statisticians.

 

The most recent critical analysis of the published antidepressant

children trial reports by an independent team of Australian and

British analysts refutes the claimed positive findings of the company-

paid psychiatrists.

See: Jon N Jureidini, Christopher J Doecke, Peter R Mansfield,

Michelle M Haby, David B Menkes, Anne L Tonkin, Efficacy and safety

of antidepressants for children and Adolescents by BMJ, online at:

http://bmj.bmjjournals.com/cgi/content/full/328/7444/879

<http://bmj.bmjjournals.com/cgi/content/full/328/7444/879> ?

 

The New York Times reports, " Dr. Temple was unapologetic about the

decision " to embargo the Mosholder report, and " The agency declined

to make Dr. Mosholder available for an interview. " The Chronicle

reports, " Despite repeated requests, senior FDA officials declined to

comment for this story. "

 

 

Below excerpts from The San Francisco Chronicle and The New York

Times.

 

See also: The NJ Star Ledger. FDA denies silencing reviewer BY ED

SILVERMAN, http://www.nj.com/search/index.ssf?/base/business-

0/1082098358140500.xml?sta

rledger?bpha

See also: AP Breaking News, House committee to investigate FDA's

review of antidepressants and their possible link to suicide in

children by Lauran Neergaard, Thursday, April 15, 2004

 

Contact: Vera Hassner Sharav

Tel: 212-595-8974

e-mail: veracare

 

<http://www.sfgate.com/cgi-bin/article.cgi?

file=/chronicle/archive/2004/04/1

6/MNGQN668FL1.DTL>

 

FDA was urged to limit kids' antidepressants Advice citing risk of

suicide rejected Rob Waters, Special to The Chronicle

Friday, April 16, 2004 Page A - 1

 

-----cut ---

Dr. Andrew Mosholder, an epidemiologist in the FDA's Office of Drug

Safety, analyzed 22 clinical trials of nine antidepressants and

concluded that the drugs appeared to double the risk of suicidal

behavior among children. A copy of his report, obtained by The

Chronicle, shows that Mosholder recommended that the FDA adopt

a " risk management strategy directed at discouraging off-label

pediatric use of antidepressants " other than Prozac in the treatment

of children with depression.

As reported by The Chronicle at the time, Mosholder's presentation to

an FDA advisory committee in February was removed from the agenda by

his superiors at the agency.

 

The FDA opted not to issue a recommendation to doctors that they stop

prescribing the drugs to children, as British regulators did last

year and as Mosholder had urged. Instead, the agency took a much

milder step last month and called on drug companies to include

warnings in the prescribing information provided to doctors about the

risks of negative side effects among patients who start taking a drug

or increase its dosage.

 

The agency also contracted with a group of doctors at Columbia

University to reanalyze the clinical trial data provided by drug

companies, the same data Mosholder reviewed, to see whether suicidal

events were correctly classified. Agency officials have argued that

the data from those trials are sometimes vague and that some

behaviors -- such as a child slapping herself in the head -- may have

been labeled wrongly as suicidal events by researchers conducting the

drug company-funded studies.

 

Committees in both the House and Senate have opened investigations

into the withholding of Mosholder's report and into efforts by the

FDA's Office of Internal Affairs to identify the staff members who

leaked information to The Chronicle. One congressional source

predicted that the investigation was likely to trigger congressional

hearings. " I think eventually there will be some hearings, " the

source said. " There's no way to put a good face on this decision not

to allow Dr. Mosholder to present his conclusions to the advisory

committee. "

 

---cut ---

....in a letter sent Wednesday to House Energy and Commerce Committee

Chairman Joe Barton, R-Texas, an agency representative defended the

agency's decision to keep Mosholder from presenting his report.

Agency officials " decided that having Dr. Mosholder present his

conclusion to the Advisory Committee, with the appearance that it was

an agency determination, would be potentially harmful to public

health as it might lead patients who were actually benefiting from

the use of these drugs to inappropriately discontinue therapy, " wrote

Amit Sachdev, acting associate commissioner for legislation.

 

Critics of the FDA's handling of the antidepressant ruling reacted to

details of the Mosholder report with outrage. " It's astounding that

FDA officials actively blocked vital, possibly life-saving

information about the suicide risks to children " of these drugs, said

Vera Sharav, president of the Alliance for Human Research Protection,

an advocacy group. " Every day that doctors and parents are not

informed about the risks, children are at risk of dying. "

 

In arguing that the agency should take strong action rather than wait

for the reanalysis by the Columbia University group, Mosholder made

much the same point in his report.

" Given the strength of the association shown by the present data, the

clinical importance of the apparent effect, and the fact that the

additional analyses are likely to take several more months to

complete while considerable numbers of pediatric patients are being

exposed to these drugs, I favor an interim risk management plan, " he

wrote.

 

Mosholder's report found that 74 children out of 2,298 who took

antidepressants engaged in a " suicide-related event, " compared to 34

of the 1, 952 patients who took placebos, or fake pills. The drugs

presenting the highest risk were Effexor and Paxil, which nearly

tripled the risk of a suicidal event, and Zoloft, which more than

doubled the risk, his research showed. .cut..

 

Joseph Glenmullen, a clinical instructor in psychiatry at Harvard

University, said the agency's withholding of the Mosholder report and

its failure to take stronger action was an example of the FDA's

failure to protect the public from the dangerous side effects of

antidepressants. " They have mishandled this issue for 15 years, " he

said. " They have not adequately protected American children. "

 

C2004 San Francisco Chronicle

~~~~~~

 

http://www.nytimes.com/2004/04/16/politics/16DEPR.html?hp

<http://www.nytimes.com/2004/04/16/politics/16DEPR.html?hp>

 

THE NEW YORK TIMES

April 16, 2004 A-16

Expert Kept From Speaking at Antidepressant Hearing By GARDINER

HARRIS

 

Top Food and Drug Administration officials admitted yesterday that

they barred the agency's top expert from testifying at a public

hearing about his conclusion that antidepressants cause children to

become suicidal because they viewed his findings as alarmist and

premature.

 

" It would have been entirely inappropriate to present as an F.D.A.

conclusion an analysis of data that were not ripe, " Dr. Robert

Temple, the Food and Drug Administration's associate director of

medical policy, said in an interview. " This is a very serious matter.

If you get it wrong and over-discourage the use of these medicines,

people could die. " Dr. Temple was seeking to quell a growing

controversy into whether the agency's warnings on March 22 that

antidepressant therapy could lead patients to become suicidal were

sufficient.

 

" There is concern that we hid data, " said Dr. Temple. " We did not

hide data. It was there for all to see. " Recent studies have shown

that children given antidepressants are more likely to become

suicidal than those given placebos. But the studies have lead to

different interpretations by psychiatrists. The refusal by drug

companies to publish the studies has worsened the confusion. Internal

agency documents obtained by The New York Times show that federal

health officials are divided, too.

 

Dr. Andrew D. Mosholder, an agency epidemiologist, was the man

charged with analyzing 22 studies involving 4,250 children and seven

drugs. In a carefully argued, 33-page memorandum, he concluded that

children given antidepressants were almost twice as likely as those

given placebos to become suicidal.

 

He urged the agency to discourage doctors from prescribing to

children all antidepressants except Prozac. Prozac is the only

antidepressant proven effective in treating depressed children, and

its studies showed no link with suicide, Dr. Mosholder wrote. Dr.

Mosholder's conclusions mirrored those made by British health

authorities.

But Dr. Mosholder's supervisors, Drs. Mark Avigan and Anne Trontell,

wrote memorandums disagreeing, according to the documents.

" In particular, we disagree that the data are sufficiently robust

to advocate preferential use of " Prozac in children, Dr. Trontell

wrote.

 

Health officials convened a special advisory committee on Feb. 2 to

offer guidance on how the agency should respond to the studies. As

the agency's principal reviewer, Dr. Mosholder was scheduled to

speak. He was removed from the agenda, Dr. Temple said.

 

Senator Charles E. Grassley, a Republican from Iowa and chairman of

the Senate Finance Committee, said he was investigating whether the

agency inappropriately suppressed crucial findings. Representative

Joe L. Barton, a Republican from Texas who is chairman of the House

Energy and Commerce Committee, said he was also investigating.

" It would have been very wrong for the F.D.A. to withhold any

information it had about unintended consequences that might result

from the use of antidepressants, especially for children and

adolescents, " Mr. Grassley said.

 

Dr. Temple was unapologetic about the decision. He said that Dr.

Mosholder's underlying data were presented to the committee but that

agency officials explained that Dr. Mosholder had failed to treat

with the appropriate skepticism some reports of suicidal behavior.

The Food and Drug Administration has hired investigators at Columbia

University to examine reports from about 400 of the 4,250 children

and determine independently which should be classified as suicidal.

 

The controversy had its start when GlaxoSmithKline sought a six-month

extension to its patents on Paxil. To help guide pediatricians'

prescribing habits, federal law grants such extensions when companies

test their medicines in children.

 

The company's studies in depressed children failed to show any

positive effect. It was a disappointing finding, but patent

extensions are granted even when studies fail. Reviewing the data,

Dr. Mosholder noticed in October 2002 that they showed a disturbing

number of problems listed under the category, " emotional liability. "

Suicidal thoughts and self-injurious behavior were among the things

lumped into this category. Dr. Mosholder asked GlaxoSmithKline to

provide more detail about these cases, according to one of the

documents.

 

In May 2003, the company submitted a new report. It showed that

children given Paxil were more likely to become suicidal than those

given placebos. In June, the agency announced that doctors should

avoid using Paxil in depressed children.

Three days later, according to documents and interviews, the agency

asked for similar data from the makers of Prozac, Zoloft, Luvox,

Celexa, Wellbutrin, Effexor, Serzone and Remeron.

Dr. Mosholder found that 108 of the 4,250 children had done

something that merited being called suicidal. He divided the cases

into those who were given drugs and those given placebos and found

that children given drugs were almost twice as likely to become

suicidal as those given placebo.

 

The agency declined to make Dr. Mosholder available for an interview.

 

Copyright 2004 The New York Times Company

 

~~~~~~~~~~~~~

 

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