1
DEPARTMENT OF HEALTH AND HUMAN
SERVICES
FOOD AND DRUG
ADMINISTRATION
CENTER FOR DRUG EVALUATION AND
RESEARCH
JOINT MEETING OF THE
CDER PSYCHOPHARMACOLOGIC DRUGS
ADVISORY COMMITTEE
AND THE
FDA PEDIATRIC ADVISORY
COMMITTEE
Holiday Inn Bethsda
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PARTICIPANTS
PSYCHOPHARMACOLOGIC DRUGS ADVISORY
COMMITTEE MEMBERS:
Wayne K. Goodman, M.D., Chair
Jean E. Bronstein, R.N.,
M.S.
(Consumer Representative)
James J. McGough, M.D.
Philip S. Wang, M.D., M.P.H., Dr.P.H.
Lauren Marangell, M.D.
Dilip J. Mehta, M.D., Ph.D.
(Industry Representative)
Delbert G. Robinson, M.D.
Daniel S. Pine, M.D.
Barbara G. Wells, Pharm.D.
Bruce G. Pollock, M.D., Ph.D.
PEDIATRIC ADVISORY
COMMITTEE MEMBERS:
P. Joan Chesney, M.D., Chair
Deborah L. Dokken, M.P.A.
Michael E. Fant, M.D., Ph.D.
Richard L. Gorman, M.D.
Robert M. Nelson, M.D., Ph.D.
Thomas B. Newman, M.D., M.P.H.
Judith R. O'Fallon, Ph.D.
Victor M. Santana, M.D.
CONSULTANTS AND GUESTS (Voting):
Norman Fost, M.D., M.P.H.
Charles E. Irwin, Mr., M.D.
Laurel K. Leslie, M.D., F.A.A.P.
Steven Ebert, Pharm.D. (Consumer
Representative)
James M. Perrin, M.D.
Cynthia R. Pfeffer, M.D.
Gail W. Griffith
(Patient Representative, Voting)
Robert D. Gibbons, Ph.D.
Tana A. Grady-Weliky, M.D.
Richard P. Malone, M.D.
Irene E. Ortiz, M.D.
Matthew V. Rudorfer, M.D.
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PARTICIPANTS
(Continued)
GUEST SPEAKERS AND GUESTS (Non-Voting):
Kelly Posner, Ph.D.
John March, M.D., M.P.H.
Samuel Maldonado, M.D.,
M.P.H.
(Industry Representative
Barbara Stanley, Ph.D.
Madelyn Gould, Ph.D., M.P.H.
FDA PARTICIPANTS:
Robert Temple, M.D.
Russell G. Katz, M.D.
Thomas Laughren, M.D.
M.
Dianne Murphy, M.D.
Anne Trontell, M.D., M.P.H
Anuja M. Patel, M.P.H., Executive Secretary
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C O N T E N T S
Call to Order and Opening
Remarks,
Wayne Goodman, M.D. 6
Introduction of Committee 9
Conflict of Interest Statement,
Anuja Patel, M.P.H. 20
Overview of Issues:
Dianne Murphy, M.D., Director, Office
of
Pediatric Therapeutics,
Office of the Commissioner 25
Russell Katz, M.D., Director, Division
of
Neuropharmacological Drug Products,
DNDP, CDER 34
Regulatory History and Background,
Thomas Laughren, M.D., Team Leader,
DNDP, CDER 46
Recent Observational Studies of
Antidepressants
and Suicidal Behavior,
Diane Wysowski, Ph.D., Division of
Drug Risk
Evaluation, Office of Drug Safety,
CDER 62
Brief Report on TADS Trial,
John March, M.D., M.P.H., Duke
University 74
Committe Discussion on TADS Trial 93
Characteristics of Pediatric
Antidepressant Trials,
Greg Dubitsky, M.D., Medical Officer,
DNDP, CDER 107
Classification of Suicidality Events,
Kelly Posner, Ph.D., Columbia
University 117
OCTAP Appraisal of Columbia
Classification
Methodology,
Solomon Iyasu, M.D., M.P.H., Team
Leader,
Office of Counter-Terrorism and
Pediatric
Drug Development 140
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C O N T E N T S
(Continued)
Results of the Analysis of Suicidality in
Pediatric
Trials of Newer Antidepressants,
Tarek Hammad, M.D., Ph.D., M.Sc.,
M.S., Senior
Medical Reviewer, DNDP, CDER 152
Comparison Between Original ODS and DNDP
Analyses
of Pediatric Suicidality Data Sets,
Andrew Mosholder, M.D., M.P.H.,
Division of
Drug Risk Evaluation, ODS, CDER 200
Citalopram and Escitalopram Product
Safety Data,
Jeffrey Jonas, M.D., Forest
Laboratories, Inc. 219
Sertraline Use in Pediatric Population: A
Risk/Benefit Discussion,
Steven J. Romano, M.D., Pfizer,
Inc. 232
Wyeth Pharmaceuticals, Joseph S. Camardo,
M.D. 247
Open Public Hearing 255
Summary by the Committee Chair 444
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P R O C E E D I N G S
Call to Order and Opening
Remarks
DR. GOODMAN: I wish to welcome you to
this two-day joint session of the
Psychopharmacologic Drugs Advisory Committee
and
the Pediatric Advisory Committee, being
held on
September 13th and 14th here, at the
Holiday Inn in
Bethesda, Maryland.
I am Wayne Goodman, Professor
of
Psychiatry at the University of Florida,
today
wearing my hat as chair of the advisory
committee.
As you settle in, please take this
opportunity to
put into silent mode your cell phones and
any other
devices that emit sounds in the audible
range of
human beings.
Some of you may be surprised not to see
Matt Rudorfer in this seat but we
arm-wrestled for
the position and he won.
[Laughter]
In all seriousness, his term
has ended but
we are fortunate to see him return as a
voting
consultant to the committee.
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I have some official language
to read to
you.
All committee members and consultants have
been provided with copies of the background
materials, from both the sponsors and the
FDA, and
with copies of letters from the public
that we
received by the August 23rd
deadline. The
background materials have been posted on the
FDA
website.
Copies of all these materials are
available for viewing at the FDA desk
outside this
room.
We have a very large table, a
full house
and important topic today so I would like
to start
with a few rules of order. Please speak directly
into the mike when called on. We will be keeping
track of individuals at the table who
wish to speak
and we will call upon them in order.
FDA relies on the advisory
committee to
provide the best possible scientific
advice
available to assist us in the discussion
of complex
topics.
We understand that issues raised during
the meeting may well lead to
conversations over
breaks or during lunch. However, one of the
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benefits of an advisory committee meeting
is that
the discussions take place in an open and
public
forum.
To that end, we request that members of the
committee not engage in off-record
conversations on
today's topic during the breaks and
lunch.
Whenever there is an important
topic to be
discussed there are a variety of
opinions. One of
our goals today and tomorrow is for the
meeting to
be conducted in a fair and open way where
every
participant is listened to carefully and
treated
with dignity, courtesy and respect. Anyone whose
behavior is disruptive to the meeting will
be asked
to leave.
We are confident that everyone here is
sensitive to these issues so understand
that these
comments are as a gentle reminder.
We look forward to a productive
and
interesting meeting. This is an unusual meeting in
that we have two advisory committees
represented
here, Psychopharmacological Drugs
Advisory
Committee, chaired by myself, and the
Pediatric
Advisory Committee, chaired by Joan
Chesney, to my
left. We will now go around the table and have the
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committee introduce themselves, starting
on my
right.
Please indicate your expertise and
affiliation. We will start in that corner, over
there.
Introductions
DR. TEMPLE: Bob Temple.
I am the Office
Director, ODE I.
DR. KATZ: Russ Katz, Division Director,
Division of Neuropharmacological Drug
Products,
FDA.
DR. LAUGHREN: Tom Laughren, phychopharm.
team leader, in the Neuropharmacological
Division.
DR. MURPHY: Dianne Murphy, Office
Director, Office of Pediatric
Therapeutics.
DR. TRONTELL: Anne Trontell, Deputy
Director, Office of Drug Safety.
DR. FANT: I am Michael Fant, University
of Texas Health Science Center in
Houston. My
expertise is neonatology and
biochemistry.
DR. PFEFFER: Cynthia Pfeffer. I am a
child psychiatrist at Weill Medical
College of
Cornell University, and I have expertise
in
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depression suicidal behavior in children
and
adolescents.
DR. FOST: Norm Fost, University of
Wisconsin, Professor of Pediatrics,
Director of the
Bioethics Program and Chair of the IRB.
DR. ORTIZ: Irene Ortiz, University of New
Mexico, Albuquerque VA. My expertise is in
depression in the elderly.
DR. MALONE: Richard Malone, Drexel
University College of Medicine, and my
area is
child psychiatry.
DR. NELSON: Robert Nelson, Children's
Hospital of Philadelphia and the
University of
Pennsylvania. My expertise is in pediatric
critical care medicine and ethics.
DR. PERRIN: Jim Perrin, Professor of
Pediatrics, Harvard Medical School and
Head of the
Division of General Pediatrics at the
Mass. General
Hospital.
I have shortened my expertise as being
in general pediatrics.
DR. GRADY-WELIKY: Tana Grady-Weliky,
Associate Professor of Psychiatry at the
University
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of Rochester School of Medicine and
Dentistry. My
expertise is in mood disorders and women
across the
reproductive life cycle and medical
education.
DR. EBERT: Steven Ebert, Department of
Pharmacy of Meriter Hospital and School
of
Pharmacy, University of Wisconsin,
Madison.
DR. GIBBONS: Robert Gibbons, Professor of
Statistics and Professor of Psychiatry
and Director
of the Center for Health Statistics at
the
University of Illinois, Chicago. I only do math!
DR. PINE: Danny Pine, child and
adolescent psychiatrist, National
Institute of
Mental Health intramural research
program. I am a
clinical child psychiatrist.
MS. BRONSTEIN: Jean Bronstein,
psychiatric nurse, Stanford University
Hospital,
the consumer representative.
DR. RUDORFER: Matthew Rudorfer, National
Institute of Mental Health. My areas of expertise
are mood disorders and
psychopharmacology.
MS. PATEL: Anuja Patel, Advisors and
Consultants Staff, Executive Secretary
for the
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Psychopharmacologic Drugs Advisory
Committee.
DR. CHESNEY: Joan Chesney, the University
of Tennessee, in Memphis, and Professor
of
Pediatrics, and my specialty is
infectious
diseases.
DR. MCGOUGH: Jim McGough, Professor of
Psychiatry, UCLA. My area is child and adolescent
psychopharmacology.
MS. GRIFFITH: My name is Gail Griffith
and I serve as the patient rep. on this
committee,
and I would just like to take this
opportunity to
say why I am here. First, I am not a medical
professional; I am a consumer. I have suffered
from major depression since I was a
teen. Second,
I have a son who suffers from major
depression and
three years ago, at age 17, after he was
diagnosed
and placed on a regimen of
antidepressants he
attempted suicide by overdosing
intentionally on
all his medications. He nearly died. So, I know
this illness. I know what it does to adolescents.
For the record, I would simply
like to
state that I have no professional ties to
any
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advocacy group or any patient
constituency. I also
wish to affirm that I have no ties to any
pharmaceutical company, nor do I hold any
investments in pharmaceutical
manufacturers. My
sole responsibility is to ensure that the
interests
of concerned parents and families are
represented
at this meeting.
DR. MARANGELL: Lauren Marangell, Baylor
College of Medicine. I specialize in adult
interventions in mood disorders, both
unipolar and
bipolar.
DR. ROBINSON: I am Delbert Robinson. I
am from the Albert Einstein College of
Medicine, in
New York, and I specialize in psychotic
disorders
and anxiety disorders.
DR. LESLIE: Laurel Leslie. I am a
behavioral developmental pediatrician at
Children's
Hospital, San Diego and my area of
expertise is in
children's mental health services
research.
DR. IRWIN: Charles Irwin. I am a
professor of pediatrics at the University
of
California, San Francisco. I am in charge of the
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Division of Adolescent Medicine at the
University,
which is a multi-disciplinary program
that cares
for adolescents and trains large numbers
of
individuals caring for teenagers, and my
research
is in the area of risk-taking during
adolescence.
MS. DOKKEN: I am Deborah Dokken. I
reside in the Washington, D.C. Metro
area. I do