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I wonder if the 16 pages includes the 4 that went missing. Zee

Eli Lilly Goes
On the Offensive
To Defend Prozac

By LEILA ABBOUD
Staff Reporter of THE WALL STREET JOURNAL
January 13, 2005; Page D3

Eli Lilly & Co. gave regulators detailed documents to rebut allegations
made by a prominent British medical journal that it concealed data
linking its antidepressant Prozac to increased risk of suicide.

Lilly produced and submitted to the Food and Drug Administration 16
pages of annotations and explanations for documents that the British
Medical Journal used to make its allegations. In the annotations, the
company charted out a chronology of its multiple submissions and
communications with health regulators to make the case that it had been
forthcoming about Prozac side effects. Lilly identified what the
documents were, when they were written and by whom, and what was done
with them, information that had been missing.

The BMJ said it couldn't comment because it hadn't seen Lilly's
response to the documents.

The flap began when the BMJ published an article Jan. 1 saying it had
given the FDA copies of confidential Eli Lilly internal documents that
showed the company long had known about troubling side effects and
played down the risks. The BMJ also quoted an FDA reviewer who worked
on the Prozac application as saying he wasn't given the data.

The BMJ said it obtained the documents, which emerged from a product
liability lawsuit in the 1980s, from an anonymous source. They later
were made public by Rep. Maurice Hinchey (D., N.Y.), who is
investigating the allegations.

Lilly said it hit back because the BMJ article was inaccurate and
widely covered in the media. The company plans to publish an "open
letter" to doctors and patients in national newspaper advertisements
today to dispute the reports. "The BMJ published an inaccurate and
misleading report on Prozac," said Greg Brophy, Lilly's director of
U.S. regulatory affairs. "Lilly wants to set the record straight."

The public battle between Lilly and the BMJ comes at a time when issues
of drug safety and clinical trial disclosure are in the spotlight. The
FDA has been criticized for being too lax in its oversight, and a
top-selling arthritis drug was removed from the market because of links
to cardiac problems. The FDA, after an intense public debate, also
recently issued a warning that antidepressants sometimes can cause an
increased risk of suicidal thinking and behavior in children with
depression and other psychiatric disorders.

Lilly specifically disagreed with the BMJ's central allegation that
Lilly hid a 1988 internal memo that reported that Prozac caused 38% of
patients in clinical trials to experience "activation," a clinical term
used to describe nervousness, agitation or insomnia, compared with 19%
in the placebo group. Because "activation" can be a marker of increased
risk of suicide, such data are central to whether the drug causes
violent tendencies.

Lilly said the charge that it had concealed the information was wrong
because it had published five articles in peer-reviewed medical
journals on the issue of activation and Prozac, some of which showed up
to 40% rates of activation.

"It's absurd to say that we weren't forthcoming on data on activation
and agitation," said Alan Breier, Lilly's chief medical officer. "Every
bit of data we've had on agitation that has any relevance whatsoever
has been published."

Lilly also singled out five pages of charts included in the documents
used by the BMJ that were widely reported in the media as showing that
Prozac caused suicidal thoughts and behaviors far more often than the
older antidepressants in use at the time. Lilly said the slides
actually were prepared by an FDA official and presented at a 1991
advisory-panel meeting held to evaluate Prozac's possible link to
increased risk of suicide. A FDA spokeswoman confirmed that the slides
were made by someone at the FDA.
Write to Leila Abboud at leila.abboud@wsj.com1