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Some critics, however, have argued that medical journals
themselves have been a part of the problem. A growing number of
studies in recent years have shown that journals publish more trials
with positive results than those with negative or inconclusive ones.
And critics say the journals have moved too slowly to address such
Dr. Catherine D. DeAngelis, the editor of The Journal of the
American Medical Association, said the idea of requiring trial
registration had been kicking around among editors for about a
decade. She said the issue came up again during a discussion at a
meeting earlier this month of the International Committee of Medical
Journal Editors, partly out of frustration.
"We have tried editorials," said Dr. DeAngelis. "We tried getting
the pharmaceutical companies to do it. We tried talking to leaders
in government. But it hasn't happened."
While Dr. Drazen and Dr. DeAngelis said their group was likely to
decide over the coming months what course to follow, it is not clear
how the drug industry will react. Last week, Merck
said it would support the idea of a government-run test registry.
said it would soon begin posting on its company Web site the trial
results of all its drugs on the market, including tests for
potential new uses of them.
Some other companies and the drug industry's trade group, the
Pharmaceutical Research and Manufacturers Association of America,
said last week that they could not comment because they had not seen
specific registry proposals. But one official of the trade group
raised concerns that registries could release company trade secrets
or present data in ways confusing to doctors and the public.
Whatever the case, the example of the little-known test of Celexa
in adolescents shows how medical journals can now miss information
about a major trial of a drug that is the subject of an article.
Dr. Nancy C. Andreasen, the editor of The American Journal of
Psychiatry, which is the flagship publication of American
Psychiatric Association, said it was the responsibility of a study's
authors to provide a scholarly overview of the published articles
discussed in their paper. She said that her publication did not
specifically ask authors or companies that sponsor trials about
"We didn't have a checklist that includes that question," Dr.
Andreasen said. She added, though, that the publication regularly
reviews its policies.
The Celexa trial in question was run in Europe from 1996 to 2002
and was sponsored by H. Lundbeck, the Danish company that developed
Forest Laboratories sells the drug, which is generically known as
citalopram, in this country under a license with Lundbeck.
A spokesman for Lundbeck said the company reported the trial
results to Forest, although he could not say when. Forest executives
did not respond to written inquiries from The Times seeking that
But Forest executives apparently had an opportunity to know about
the European test before the publication of the positive trial's
results this month in The American Journal of Psychiatry. Forest
executives said they presented safety data concerning potential
suicide risk from both the positive study and the European trial
last fall at a medical conference. It was around that time that
regulators in Britain and this country expressed concerns that
several antidepressants might cause some depressed teenagers to
consider suicide; the issue is still under study.
The Lundbeck spokesman said that an abstract about the European
trial had been presented in April at a Swedish medical meeting, and
both companies said that an article about that trial was being
prepared for publication. Both companies also said that they did not
promote the drug's use in children because regulators had not
approved it for pediatric use. (Doctors can legally prescribe a drug
for any use, once it has been approved for at least one
Dr. Andreasen and other journal editors interviewed said that a
single failed trial of a drug did not mean that the treatment was
ineffective, because the study's design might have been flawed. By
the same token, of course, a single positive test of a drug does not
necessarily mean that it works.
In a Lancet article in April, British researchers sought to
compare the benefits and risks that widely used antidepressants pose
for children and adolescents, based on published and unpublished
data. They reported that their analysis of the pooled results from
two unpublished Celexa trials - the one since published in The
American Journal of Psychiatry and the European study cited in the
Danish textbook - suggested that citalopram was unlikely to produce
a "clinically important reduction in depressive symptoms."
"With no good evidence for efficacy and the potential for
increasing the risk for suicide, the risk-benefit balance is
unfavorable," the researchers reported.
Dr. Karen Dineen Wagner of the University of Texas Medical Branch
in Galveston, who was the lead outside investigator on the study
published in The American Journal of Psychiatry, did not respond to
interview requests through a hospital spokeswoman. The two other
outside researchers involved, however, both said that Celexa worked
well in their test and that the young patients did not experience
increased suicidal thoughts.
"I don't know what the raw data looks like from the European
study," said one of them, Dr. Adelaide S. Robb of the Children's
National Medical Center in Washington.
She said that she was informed by Forest executives in 1999 that
the European study was under way but that she was never told that it
had been completed.