[SSRI-Research] HMO physician applauds Spitzer's focus on information bias / NYT blind spot

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Mon, 21 Jun 2004 03:00:49 -0000

[sSRI-Research] HMO physician applauds Spitzer's focus on information

bias / NYT blind spot

 

The affirmation by a Kaiser Permanente physician, Dr. Kate Scannell,

that NYS Attorney General, Eliot Spitzer, deserves applause for

his " bold and courageous " lawsuit, is an encouraging watershed. The

suit, she says, " gives me hope that we may be nearing high noon in

New York, about to witness an overdue showdown between the commercial

interests of the drug marketplace and the health interests of

humanity that drug science should serve. "

 

Dr. Scannell reminds us: " The human stakes in this case are

considerable, because researchers elsewhere have raised serious

concerns that some antidepressants might actually increase the risk

of suicide in children. Moreover, about 2.1 million paroxetine

prescriptions were written for children in 2002. "

 

She urges the medical community and the FDA to come to Spitzer's

assistance because " he will need a good many deputies to help him. "

Recently uncovered evidence, however, shows that senior FDA officials

have suppressed a report by Dr. Andrew Mosholder, FDA's top expert

whose recommendations to discourage the use of antidepressants in

children, the Times reports: " would have been a monumental step.

Antidepressants are among the biggest-selling drugs in the world and

have long been viewed by doctors as relatively safe. Their use in

children has been soaring. "

 

FDA's action to muzzle Dr. Moshlolder put greater value on protecting

profits than children's lives. In essence, FDA officials have been

complicit in industry's research concealment practices. When the

concealed data revealed drug hazards, the FDA and the psychiatric

establishment raised a straw man, seeking to redefine suicidal

behavior. See Senator Chuck Grassley's June 3, 2004, letter to FDA's

acting commissioner and Secretary of Health and Human Services, Tommy

Thompson requesting all pertinent documents, including e-mail

communication between FDA officials and drug company officials:

http://finance.senate.gov/press/Gpress/2004/prg060304.pdf

 

 

In sharp contrast to the sobering reality checks by Senator Grassley

and Attorney General Spitzer, a report in today's New York Times

fails to delve beneath the surface. The Times article fails to report

institutional conflicts of interest--no matter how significant.

 

University-affiliated psychiatrists may pretend naiveté by

claiming: " We're just dealing with a lot of pieces of paper. We're

not dealing with people at all. " But an examination of their

contractual agreements will reveal that they do not in fact, function

in a pristine bubble. FDA's choice of Columbia University as arbiters

in the controversy over interpretation of evidence of suicidal

behavior in children prescribed an antidepressant is being challenged.

 

Shouldn't a NY Times business reporter find out how much money

Columbia and its department of psychiatry garnered within the last 15

years from pharmaceutical companies (and industry-supported

foundations) for psychiatric drug research?

 

Similar data should be obtained for other major psychiatric drug

research centers, including: NYU, U Pittsburgh, UCLA, Johns Hopkins,

U Maryland, U Texas.

 

AHRP questions:

* the impartiality of Columbia employees inasmuch as the university

receives substantial support from drug manufacturers;

* the professional standards of those who claim that they can second

guess from afar the difference between self-destruction and suicidal

intent of children they have never met;

* the motives of psychiatrists who are eager to sit in judgment of

the professional judgment of those who had first hand knowledge of

these children's behavior;

* the selection of psychiatrists who raised no objections to data

concealment or tainted published reports.

 

Earlier this month, the Times reported, without documented evidence,

that a new, unpublished Prozac trial in adolescents showed positive

findings. But the Times did not see fit to report that a fully

documented independent analysis comparing published and unpublished

pediatric antidepressant trial data, published in The Lancet, found

children at significant increased risk of suicidal behavior when

prescribed an SSRI antidepressant compared to placebo.

See: http://www.thelancet.com/journal/journal.isa

 

 

Contact: Vera Hassner Sharav

Tel: 212-595-8974

e-mail: veracare

 

http://www.timesstar.com/Stories/0,1413,125%257E1511%

257E2224675,00.htm

 

TIMES STAR

 

It's time to focus on information bias about drugs

 

By Dr. Kate Scannell

Sunday, June 20, 2004 -

 

HEARING about an exciting new drug study can make a pill sound so

fantastic that we can hardly wait to take it. We rush to our doctor's

office to show her the newspaper clippings, and for extra measure we

bring along a few supporting documents that we have downloaded from

the Internet.

 

But suppose that one glorious study we heard about was just that --

the one glorious study about that drug. Suppose that there existed

three or four additional studies that made that drug seem undesirable

or, at least, inglorious, and we had no way of knowing about them.

Suppose those hidden studies contained information about side effects

or contradictory data that suggested the drug really didn't work.

 

It's unsettling to consider these possibilities, but it's important

to remain vigilant about them. Clinically important -- and generally

unfavorable -- information about drugs is often buried in publicly

inaccessible archives. Our medical journals tend not to publish

studies about drugs that were found to be duds in clinical trials.

 

Hidden drug data poses a serious and pervasive problem. For example,

a recent study in the Journal of the American Medical Association

analyzed 102 drug trials and found that 50 percent of efficacy data

and 65 percent of harm outcomes were only partially reported.

 

In certain circumstances, the suppression of drug information can be

heavy-handed. Researchers conducting trials funded by drug companies

have been required to sign contracts that grant the companies the

right to control which results get submitted for publication. A few

years ago, a vaccine manufacturer even filed a multimillion-dollar

lawsuit against a team of AIDS researchers who insisted on publishing

results from a clinical trial that found the company's HIV vaccine to

be worthless.

 

Furthermore, because there is no one place where all data about drug

trials and their results are stored, it becomes a bit of a scavenger

hunt to find all knowable information about a drug that might

interest you. This is not a healthy system when you don't know where

to look for drug information, and you can't telepathically access

what's been kept out of publication.

 

A lawsuit filed this month in New York promises to challenge the

formidable power of the pharmaceutical companies to pick and choose

the information that gets disseminated and promoted in the public

domain. New York Attorney General Eliot Spitzer has decided to sue

drug manufacturer GlaxoSmith-Kline PLC, claiming that it committed

consumer fraud by misrepresenting and withholding data about the use

of its antidepressant paroxetine (Paxil) in children.

 

The human stakes in this case are considerable, because researchers

elsewhere have raised serious concerns that some antidepressants

might actually increase the risk of suicide in children. Moreover,

about 2.1 million paroxetine prescriptions were written for children

in 2002.

 

Mr. Spitzer alleges that the drug manufacturer skewed information

about paroxetine by widely disseminating the single study that was

able to showcase the drug in a positive light. He charges Glaxo with

suppressing four other studies conducted on children and adolescents

in the late 1990s that found paroxetine to be either ineffective or

suspect for increasing the potential risk of suicide.

 

According to the Associated Press, the lawsuit also exposes an

internal Glaxo document indicating that the company intended

to " manage the dissemination of data in order to minimize any

potential negative commercial impact. "

 

In summing up his mission, Mr. Spitzer succinctly stated his

case: " Having doctors prescribe drugs without full knowledge of

safety and efficacy is wrong. "

 

I applaud Mr. Spitzer's efforts to drive out the forces that

wittingly and unwittingly obscure or manipulate the information we

need to evaluate the safety and efficacy of drugs. But he will need a

good many deputies to help him.

 

Because the vast majority of drug trials are currently funded by the

pharmaceutical companies, he will have to persuade that industry of

the merits of his mission. If he's lucky, federal regulators like the

FDA will be armed with reporting requirements and riding at his side.

Perhaps he can commandeer the public wagons to circle tight around

the research industry, closing in with demands that it consistently

reveal and disseminate all drug trial information -- whether it is

good, neutral, or bad.

 

Hopefully, the medical community will posse up en masse. So far, the

American Medical Association and the publishers of a dozen major

medical journals have called for proposals that require drug

companies to register their studies in a central database at the

outset of their trials. We could go further and decline arrangements

with drug companies that allow them to own or silence the results of

the research trials they fund.

 

Meanwhile, Mr. Spitzer's move is bold and courageous. It gives me

hope that we may be nearing high noon in New York, about to witness

an overdue showdown between the commercial interests of the drug

marketplace and the health interests of humanity that drug science

should serve.

 

Kate Scannell is a physician with Kaiser Permanente and the author

of " Death of the Good Doctor. "

~~~~~~~

 

THE NEW YORK TIMES

June 20, 2004

Antidepressants Restudied for Relation to Child Suicide

 

By GARDINER HARRIS

 

http://www.nytimes.com/2004/06/20/national/20depress.html

 

A child stabs himself in the neck with a pencil. Another slaps

herself in the face. Is either suicidal? It is a question that has

divided psychiatrists and drug regulators the world over and goes to

the heart of a fierce controversy over whether antidepressants lead

some children to become suicidal.

 

Now four researchers at Columbia University hope to provide an

answer. By reclassifying reports of suspect or self-destructive

behavior that occurred during tests of antidepressants in youngsters,

the research team hopes to clarify whether antidepressants lead

children and teenagers to become suicidal. Officials at the Food and

Drug Administration say they will use results of the study to help

them decide, later this summer, whether the agency should discourage

doctors from prescribing the pills to youngsters.

 

The study was commissioned by top F.D.A. officials after they

rejected an analysis by one of the agency's top experts that

concluded that antidepressants could be dangerous when given to

teenagers and younger children. With such a controversial beginning,

the study is being met by fierce criticism.

 

Senator Charles E. Grassley, Republican of Iowa, issued a statement

questioning whether the study was part of an effort by the Food and

Drug Administration to suppress the truth about the risks of

antidepressants. Mr. Grassley said he was investigating the study as

part of a larger inquiry into the agency's handling of the

controversy involving antidepressants and suicide.

 

Some prominent mental-health research has questioned the study's

methodology. " You've asked the Columbia group to take data that's

suboptimal and try to come up with a conclusion, and I really doubt

that they will be able to do that,'' said Dr. Thomas R. Insel,

director of the National Institute for Mental Health. The Columbia

team plans to apply a consistent definition of ''suicidal'' to a

disparate collection of more than 400 reports of adverse behavior

that occurred in 25 clinical tests of nine antidepressants. The

tests, undertaken by drug companies, involved Prozac, Zoloft, Paxil,

Luvox, Celexa, Wellbutrin, Remeron, Serzone and Effexor. One of the

problems with the drug-company trials is that they tend to confuse

self-destructiveness with suicidal attempts, team members said in an

interview. " Suicide research has come up with a specific definition

of suicide attempts: a self-injurious behavior where there is some

intent to die,'' said Barbara Stanley, one of the researchers.

 

The team will give nine independent reviewers the descriptions that

drug-company researchers used in reporting the cases involving

adverse behavior. . The reviewers will label each event as suicidal,

nonsuicidal or indeterminate, and then give the data to federal drug

regulators for statistical analysis. Discovering intent from the

brief notes provided by the drug companies could be difficult. In a

speech before an advisory panel in February, Dr. Thomas Laughren,

leader of the F.D.A.'s psychiatric drug products group, noted that

the drug companies' descriptions were often poor. " We did not have

the level of detail in these cases that one would have liked to do a

rational classification,'' Dr. Laughren said.

 

Julie Magno Zito, an associate professor of pharmacy and psychiatry

at University of Maryland, Baltimore, predicted the Columbia team

would not be able to overcome this problem. " If a kid pierces his

neck with a pencil, that could be a violent act of self-destruction

or it could have been nothing,'' Dr. Zito said. " If the notes don't

make the intent clear, how do you interpret that?'' Dr. Zito called

the Columbia study " a fundamentally bad idea.''

 

Dr. Alan Gelenberg, head of the department of psychiatry at the

University of Arizona, said the study would provide a needed

perspective. But even those who support the study agree that it is

unlikely to change many minds on the question of whether

antidepressants should be prescribed to children. " This question will

never be settled,'' said Dr. James McGough, a professor of clinical

psychiatry at the University of California, Los Angeles. " Still, I'm

eager to see what their answer is.'' In tackling the issue, the

researchers say they understand that they are being thrust into a

maelstrom rarely seen in psychiatry. " For all of us, our anxiety

levels are higher because we know that there are people invested in

this one way or the other,'' said Dr. Madelyn Gould, professor of

clinical public health in psychiatry. " Anything that has to do with

drug treatment in kids is so emotionally charged.'' The study had its

beginnings early last year when GlaxoSmithKline submitted to federal

drug regulators the results of three trials of its Paxil

antidepressant in teenagers and other children. The company had

undertaken the studies to take advantage of a federal law that delays

by six months the introduction of cheaper, generic versions of drugs

when branded makers test medicines in children. In GlaxoSmithKline's

trials, depressed young people given Paxil fared no better than those

given placebos. It was a disappointing result for GlaxoSmithKline but

had no effect on its application for the six-month extension. Still,

a reviewer at the Food and Drug Administration noticed something

strange about the trials: teenagers given Paxil suffered more

problems of ''emotional lability,'' or instability, than those given

a placebo.

 

The reviewer, Dr. Andrew Mosholder, thought ''emotional lability''

was overly broad. He asked the company to resubmit its data, this

time using a separate category for suicide. That report, given in May

to both American and British health authorities, was alarming.

Teenagers and younger children given Paxil were much more likely to

become suicidal than those given placebos. In June, both the British

and American authorities warned doctors against prescribing Paxil to

youngsters. Worried that the problem could extend far beyond Paxil,

the F.D.A. in July asked the makers of eight other antidepressants to

submit data from their studies in youngsters.

 

In August, Wyeth issued a warning that doctors should avoid

prescribing Effexor to youngsters because it, too, seemed to cause

them to become more suicidal. By September, the agency had received

the other companies' studies. Looking at them all, Dr. Mosholder

concluded that children given antidepressants were almost twice as

likely as those given placebos to become suicidal. He suggested the

agency discourage the drugs' use in children. It would have been a

monumental step. Antidepressants are among the biggest-selling drugs

in the world and have long been viewed by doctors as relatively safe.

Their use in children has been soaring.

 

Dr. Mosholder's bosses at the Food and Drug Administration, however,

said the drug company data was inconsistent and that some events

termed ''possibly suicidal'' seemed innocent. Top agency officials

hired the Columbia researchers to review the data, and they forbade

Dr. Mosholder to speak about his conclusions to an advisory panel

reviewing the matter. The silencing of Dr. Mosholder prompted outrage

among critics of antidepressants and the ongoing investigation by

Senator Grassley. It also has fostered skepticism about the Columbia

study. Already, Internet postings are questioning the backgrounds of

the Columbia researchers. One asks whether Kelly Posner, the lead

investigator, has participated in trials financed by the drug

industry.

 

In a group interview in a conference room in the New York State

Psychiatric Institute, the researchers said they were unbiased. Dr.

Posner said that she had participated in some trials sponsored by

drug makers but never as a principal investigator. All of the trials

involved attention deficit disorder, not depression or suicide, she

said. Her three colleagues said that they had never taken part in a

drug-company trial. And they said that their study, while hugely

controversial, was relatively simple: figuring out the appropriate

labels to place on the behaviors in the individual cases. " We're just

dealing with a lot of pieces of paper,'' Dr. Gould said. " We're not

dealing with people at all. And all the interesting questions happen

once we give the data over to the F.D.A.,'' where the statistical

analysis will occur.

 

Copyright 2004 The New York Times Company

 

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