-----Original Message-----
From: FDA press releases and announcements
[mailto:[log in to unmask]] On Behalf Of Norwood, Cecilia F
Sent: Wednesday, November 17, 2004 18:01
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Subject: STATEMENT/VIOXX


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STATEMENT                 Media Inquiries:     301-827-6242
November 17, 2004         Consumer Inquiries:  888-INFO-FDA


FDA STATEMENT ON VIOXX AND RECENT ALLEGATIONS AND THE AGENCY'S CONTINUED
COMMITMENT TO SOUND SCIENCE AND PEER REVIEW

The Food and Drug Administration today released the following statement
by Acting Commissioner Dr. Lester M. Crawford:

        For the past several weeks, various allegations and
characterizations have circulated and been reported on regarding FDA's
approval and post market review of the drug Vioxx, a "Cox-2 inhibitor,"
that its sponsor, Merck, voluntarily withdrew from the market September
30th, 2004.  I am issuing this statement to further clarify the Agency's
activities in this area. It covers four topics:
*       Issues involving allegations about the performance of FDA's
Office
of Drug Safety;
*       Allegations about a scientific paper submitted to the British
medical journal, The Lancet;
*       The possible participation of Dr. Curt Furberg in an upcoming
FDA
advisory committee to discuss Cox-2 inhibitors; and
*       Further information about FDA's recent announcements to
strengthen
its safety program for marketed drugs.

        First, allegations have surfaced about the handling of the
post-market review commissioned by the FDA and managed by the Center for
Drug Evaluation's Office of Drug Safety (ODS).  In particular, there has
been concern about the process used to complete that study and publish
it, including allegations that ODS managers disagreed with the project
officer's conclusions and sought to modify them. It is critical that all
the facts be presented in this case to assure public confidence in our
drug safety programs.
        In 2001, a project officer in ODS expressed interest in a
scientific collaboration between the Office of Drug Safety and Kaiser
Permanente of Northern California on the cardiovascular safety of cox-2
drugs.  FDA provided partial funding for this pilot project in August
2001 and again a year later, and our project officer served as the
project manager.
        Last February, our project officer submitted an abstract to the
International Society for Pharmacoepidemiology (ISPE) for presentation
at the group's August meeting in Bordeaux, France.  It described the
final study population of nearly 1.4 million patents and the events
being studied, but it included no results.
        When this draft was shared with the project officer's
supervisors within ODS to obtain review and clearance on August 11th,
ODS supervisors immediately recognized the importance of the project
officer's work and the need to complete a study report for FDA review
and publication in a peer-reviewed scientific journal.
        Some FDA scientists questioned some of the conclusions in the
abstract and, as a result, the project officer voluntarily chose to
revise his conclusions, and he did so, in his own words, "without
compromising my deeply held convictions."
        This poster was presented in Bordeaux in August and discussed
publicly at that time.  When he returned, his supervisors in ODS asked
him to submit a draft report on his findings within two weeks.  It was
not submitted to the Center for review until September 30th, after Vioxx
was voluntarily withdrawn from the market. Senior drug experts in FDA
did not have this report or the underlying data prior to that time.
Second, more recently, the project officer notified his supervisors that
he had submitted his findings in a paper to The Lancet.  He did this
without going through the long-established peer review and clearance
process established for scientific papers submitted by FDA scientists.
When FDA scientists learned that this paper had been accepted for
publication in The Lancet, despite not having gone through the normal
peer review process, the director of FDA's Center for Drug Evaluation
and Research contacted the journal's editor, out of respect for the
scientific peer review process.
        Third, recently much has been made of FDA's dealings with Dr.
Curt Furberg, an expert on the design of clinical trials.  The agency
intends to discuss cox-2 inhibitors at an upcoming Arthritis Drugs
Advisory Committee meeting in early 2005.  Dr. Furberg is not an
Arthritis Drugs Committee member; however, as part of our preparatory
procedures, last week the Advisory Committee staff anticipated that Dr.
Furberg could make a valuable contribution the meeting as a consultant
and following normal operating procedures contacted him to ascertain his
availability.  Dr. Furberg discussed with a staff member his recent
activities related to the cox-2 inhibitor controversy at a recent
American Heart Association meeting.  Based on their discussion, Dr.
Furberg concluded that he would not be allowed to participate because of
potential bias.  However, the advisory committee preparation process is
still underway, so it was premature for any FDA official to suggest that
Dr. Furberg could not participate in the upcoming meeting. A decision on
Dr. Furberg's participation has not been made because all of the
relevant information is not yet available.
        Fourth, FDA has a well-documented and longstanding commitment to
openness and transparency in its review of marketed drugs.  Indeed, the
post-market review of Vioxx and antidepressants were initiated and
funded by FDA and managed by its Office of Drug Safety.  That is
evidence that the system is working.  Even so, two weeks ago I announced
additional steps to strengthen that program in the form of a major
initiative designed to improve the monitoring of drug products recently
on the market.
        The major components of that FDA initiative include:
*       Sponsoring a major study of the Drug Safety System by the
prestigious Institute of Medicine;
*       Appointing a permanent director for the Office of Drug Safety;
*       Conducting a series of workshops and meetings on drug safety and
risk management; and
*       Publishing risk management guidances

Let me emphasize the importance of scientific peer review in the
management of drug risks.  Peer review is so important that, as part of
this drug safety initiative, we are also improving our process for
ensuring that internal differences of scientific opinion are fully
incorporated into the FDA's decision-making process. Science at FDA, as
elsewhere, typically proceeds by frank discussion and open exchange,
followed by a consensus.  The organization reaches its conclusion and
everyone carries it out. There are times when honest scientific
disagreement cannot be resolved, however, and such disagreements can
have a potentially significant public health impact.  That is why our
new program provides for a review by an ad hoc panel not directly
involved in the decisions, by FDA, and by outside experts. FDA
encourages open and vigorous internal debate about the often difficult
scientific questions it routinely faces.  In the end, we must weigh the
evidence - in this case the benefits and risks of cox-2 inhibitors - and
then decide on behalf of our citizens whether the products should be
available.  It is a daunting task, and it is one that the FDA has been
-- and continues to be -- committed to carrying out every day. ####