Antidepressant makers withhold data

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Antidepressant makers withhold data

 

Info from clinical trials on children kept secret

 

http://www.msnbc.msn.com/id/4091562/

 

From washingtonpost.com

Updated: 12:18 a.m. ET Jan. 29, 2004

 

Makers of popular antidepressants such as Paxil, Zoloft and Effexor

have refused to disclose the details of most clinical trials

involving depressed children, denying doctors and parents crucial

evidence as they weigh fresh fears that such medicines may cause some

children to become suicidal.

 

The companies say the studies are trade secrets. Researchers familiar

with the unpublished data said the majority of secret trials show

that children taking the medicines did not get any better than

children taking dummy pills.

 

Although the drug industry's practice of suppressing data unfavorable

to its products is legal, doctors and advocates say such secrecy

distorts the scientific record.

 

" Conflicts of interest and the company control of the data have

thrown out the scientific method, " said Vera Hassner Sharav, a critic

of the drugs and a patients' rights advocate. " If hundreds of trials

don't work out, they don't publish them, they don't talk about them. "

 

" We need a journal of negative findings, " agreed Darrel Regier,

director of the American Psychiatric Association's division of

research, who believes the drugs save children's lives. " The

probability of those negative findings being published is far less

than the chances of positive studies -- even journals are not

interested in negative studies. "

 

Concerns over the safety of antidepressants among children have been

heightened after a December warning by British regulators that the

drugs may trigger suicidal thoughts and increase the rate of self-

injury. An expert advisory panel of the Food and Drug Administration

is scheduled to meet Monday to examine the issue, but the agency's

full U.S. analysis of the data is not likely to be completed until

summer.

 

One industry executive, Philip Perera, a medical director at

GlaxoSmithKline, said that his preference was to publish all trials

but that negative studies could lead doctors to prematurely reject a

medicine.

 

" If you start publishing negative data, will it be concluded by

practitioners and others that the drug is ineffective? " he asked,

saying that genuinely effective medicines sometimes do no better than

placebos, or dummy pills, in trials -- at least half of all children

seem to get better on placebos.

 

Maze of secret data

The U.S. psychiatric establishment largely supports the use of

antidepressant medicines in children, with many arguing that

abandoning the drugs would lead to more suicides in children with

depression. But its critics, including consumer advocates and some

psychiatrists , question whether mainstream psychiatry is biased by

widespread financial ties to the pharmaceutical industry.

 

The answer lies hidden in a maze of secret data, conflicting

scientific interpretations and a corporate-funded clinical trial

system that is not primarily designed to answer questions of public

health.

 

" If the companies wanted to publish negative studies they could, but

companies don't like to publish negative studies, " said Russell Katz,

director of the neuropharmacology division at the FDA , which has

access to all the data. " It's amusing so many people are making

pronouncements about the data -- scientists and physicians -- . . .

without seeing the data. "

 

Advocates say openness about studies is important because, apart from

Prozac, no antidepressant has been approved by the FDA for treating

children with depression. Doctors writing prescriptions do not have

approved labeling to guide them: They must rely on their own judgment

and the available scientific knowledge -- even as information is

being withheld.

 

The medicines under scrutiny belong to a class of drugs called

selective serotonin reuptake inhibitors, or SSRIs. Led by Prozac, the

first to be approved, the medicines caused a revolution in

psychiatry.

 

Recent analyses suggest that as many as 1 percent of children in the

United States are treated for depression in any year, said Mark

Olfson, a professor of clinical psychiatry at Columbia University. Of

those, 57 percent are on antidepressants.

 

The lack of information is the one issue about which advocates and

critics of the medicines agree. Lawrence Diller, a Walnut Creek,

Calif., pediatrician and author of " Should I Medicate My Child?, "

said that " as a front-line doctor dependent on research, it seems so

contaminated by potential conflicts of interest. . . . The smoking

gun is revelations from the British that negative studies were not

published. "

 

Contradictory advice

Keeping data secret, critics said, has led to conflicting

information, contradictory advice and heightened fears.

 

For example, GlaxoSmithKline, which makes Paxil, has conducted three

trials on depressed children. Company officials said all turned out

negative -- the children on the drug did not do better than those on

placebos -- but only one was published. Based on its data, the

company warned British doctors that Paxil, sold there as

Seroxat, " should not be prescribed as new therapy " to depressed

children younger than 18. Its letter last June cited the risk of

increased hostility, agitation, and suicidal thoughts and attempts.

 

No such warning was issued in the United States, though Paxil is

identical to Seroxat. Here, the company's official line on giving

Paxil to children is " No recommendations can be made regarding the

use of Paxil or Paxil CR in these patients. "

 

" There are differences " between the two recommendations,

GlaxoSmithKline's Perera acknowledged in an interview. " They reflect

the message that we receive from the respective regulatory bodies. "

British regulators have essentially prohibited the use of Paxil for

children. The FDA is conducting a review of eight drugs, including

Paxil.

 

Perera said the company would await the FDA advisory panel's verdict

before considering whether to make all its data public.

 

Cathryn Clary, vice president for psychiatry and neurology at Pfizer,

which makes Zoloft, said it had sponsored two trials in children. One

had a negative result, but the company pooled it with a positive

study and only published the combined result, which was positive.

 

" We certainly understand the wish of academics and researchers and

physicians to understand all of this data, " she said. But small

sample sizes in trials " run the risk of magnifying or diminishing a

signal. Releasing an individual study can be as misleading as it is

helpful. "

 

Graham Emslie, a professor of psychiatry at the University of Texas

Southwestern Medical Center, who has helped conduct several trials

for drug companies, counted nine recent trials of Prozac, Paxil,

Zoloft and Celexa in depressed children. Results of two Prozac

trials, one Paxil and the pooled Zoloft data have been published --

meaning that data from five trials, including the stand-alone Zoloft

trial that was negative, have not.

 

Emslie also counted six other studies on the related antidepressants

Effexor, Serzone and Remeron -- none of which has been published, he

said. Data from several of the unpublished studies have been

presented at scientific meetings, and one has been submitted for

publication, he said.

 

Studies reported at conferences are not subject to rigorous

advance " peer review " by independent researchers, as are studies

published by well-regarded journals. Emslie said he would like to see

all the data published but he said the research had been paid for --

and belongs to -- the companies. " They have a legitimate right to do

what they want with the data, " he said.

 

Public money

But David Healy, a Welsh psychiatrist and author of " The

Antidepressant Era, " rejected the notion that the safety information

could be treated like any other private property. Healy prescribes

the medicines but has campaigned for more cautious use and more

accurate labeling.

 

" On a pressing issue like this, " he said, " there is no reason these

data could not be put into the public domain in their entirety. "

 

The FDA said it is evaluating 20 studies in all, but agency officials

have declined to identify them.

 

In the end, some scientists believe, the only way to ensure that

science is conducted in the public interest is for it to be funded

with public dollars. The National Institutes of Health is therefore

ramping up funding for clinical trials.

 

" We have been dependent on the pharmaceutical industry to provide the

answers, " said Thomas R. Insel, director of the National Institute of

Mental Health. " The questions they want answered are different than

the public health questions. "

 

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