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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
CNS CLINICAL TRIALS
SUICIDALITY AND DATA COLLECTION
WORKSHOP SUMMARY
Sarah Hanson, Miriam Davis, and Bruce Altevogt, Rapporteurs
Forum on Neuroscience and Nervous System Disorders
Board on Health Sciences Policy
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, N.W.
Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This project was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; AstraZeneca Pharmaceuticals, Inc.; CeNeRx Biopharma; the Department of Health and Human Services’ National Institutes of Health (NIH, Contract No. N01-OD-4-213) through the National Institute on Aging, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the National Eye Institute, the NIH Blueprint for Neuroscience Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke; Eli Lilly and Company; GE Healthcare, Inc.; GlaxoSmithKline, Inc.; Johnson & Johnson Pharmaceutical Research and Development, LLC; Merck Research Laboratories; the National Multiple Sclerosis Society; the National Science Foundation (Contract No. OIA-0753701); the Society for Neuroscience; and Wyeth Research, Inc. The views presented in this publication are those of the editors and attributing authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
International Standard Book Number-13: 978-0-309-14883-2
International Standard Book Number-10: 0-309-14883-9
Additional copies of this report are available from the
National Academies Press,
500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu.
Copyright 2010 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
Suggested citation: IOM (Institute of Medicine). 2010. CNS clinical trials: Suicidality and data collection: Workshop summary. Washington, DC: The National Academies Press.
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
–Goethe
INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
THE NATIONAL ACADEMIES
Advisors to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
WORKSHOP ON CNS CLINICAL TRIALS: SUICIDALITY AND DATA COLLECTION PLANNING COMMITTEE*
WILLIAM POTTER (Co-chair),
Merck Research Laboratories
ROBERT GIBBONS (Co-chair),
University of Illinois at Chicago
CHARLES BEASLEY, JR.,
Eli Lilly and Company
DAVID BRENT,
University of Pittsburgh School of Medicine
YEATES CONWELL,
University of Rochester School of Medicine and Dentistry
WALTER KOROSHETZ,
National Institute of Neurological Disorders and Stroke
THOMAS LAUGHREN,
Food and Drug Administration
HUSSEINI MANJI,
Johnson & Johnson Pharmaceutical Research and Development, LLC
DAVID MICHELSON,
Merck & Co.
ATUL PANDE,
GlaxoSmithKline, Inc.
PHILIP WANG,
National Institutes of Health
IOM Staff
BRUCE ALTEVOGT,
Project Director
SARAH HANSON,
Associate Program Officer
LORA TAYLOR,
Senior Project Assistant
*
IOM planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS*
ALAN LESHNER (Chair),
American Association for the Advancement of Science
HUDA AKIL,
University of Michigan
MARC BARLOW,
GE Healthcare, Inc.
MARK BEAR,
Massachusetts Institute of Technology
DANIEL BURCH,
CeNeRx Biopharma
DENNIS CHOI,
Emory University
TIMOTHY COETZEE,
National Multiple Sclerosis Society
DAVID COHEN,
Columbia University
RICHARD FRANK,
GE Healthcare, Inc.
JOHN GRIFFIN,
Johns Hopkins University School of Medicine
RICHARD HODES,
National Institute on Aging
KATIE HOOD,
Michael J. Fox Foundation for Parkinson’s Research
STEVEN HYMAN,
Harvard University
THOMAS INSEL,
National Institute of Mental Health
STORY LANDIS,
National Institute of Neurological Disorders and Stroke
HUSSEINI MANJI,
Johnson & Johnson Pharmaceutical Research and Development, LLC
EVE MARDER,
Brandeis University
JONATHAN MORENO,
University of Pennsylvania School of Medicine
MICHAEL OBERDORFER,
NIH Neuroscience Blueprint
KATHIE OLSEN,
National Science Foundation
ATUL PANDE,
GlaxoSmithKline, Inc.
MENELAS PANGALOS,
Wyeth Research, Inc.
STEVEN PAUL,
Eli Lilly and Company
WILLIAM POTTER,
Merck Research Laboratories
PAUL SIEVING,
National Eye Institute
RAE SILVER,
Columbia University
WILLIAM THIES,
Alzheimer’s Association
NORA VOLKOW,
National Institute on Drug Abuse
KENNETH WARREN,
National Institute on Alcohol Abuse and Alcoholism
*
IOM forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
FRANK YOCCA,
AstraZeneca Pharmaceuticals, Inc.
STEVIN ZORN,
Lundbeck USA
CHARLES ZORUMSKI,
Washington University School of Medicine
IOM Staff
BRUCE ALTEVOGT, Forum Director
SARAH HANSON, Associate Program Officer
LORA TAYLOR, Senior Project Assistant
ANDREW POPE, Director,
Board on Health Sciences Policy
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this report:
Charles Beasley, Jr., Lilly Research Laboratories
Eric Caine, University of Rochester Medical Center
Joel B. Greenhouse, Carnegie Mellon University
Robert Temple, Food and Drug Administration
Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the report before its release. The review of this report was overseen by Dr. Charles F. Reynolds. Appointed by the Institute of Medicine, he was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
Contents
INTRODUCTION
1
Background on the Issues,
2
About the Forum and Workshop,
5
1
PERSPECTIVES FROM THE FDA, ACADEMIA, AND PATIENTS
7
FDA Perspective,
7
Perspective on Methodology Development and Implementation,
11
Perspective of Patients and Families,
14
2
DATA COLLECTION AND OPTIMIZATION
17
New Approaches to Studying the Predictive Power of Suicidal Ideation for Suicidality,
17
Real-Time Electronic Monitoring Systems,
19
The Predictive Validity of Suicide Ideation at Its Worst Point in Time for Suicide Attempts,
20
Neurobiological Contributions to Predicting Suicidality,
22
3
DATA ANALYSIS
25
Establishing Causal Relationships in Medicine for Public Health Policy,
25
Benefits and Limitations of Meta-Analyses,
26
Sources of Bias in Antidepressant Clinical Trials,
28
Selection Bias,
28
Regression Toward the Mean,
29
Natural Course of Illness,
30
Confounding by Indication,
30
Other Problems with Meta-Analyses,
31
Observational Studies,
33
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CNS Clinical Trials: Suicidality and Data Collection - Workshop Summary
4
PARTNERSHIPS, OPPORTUNITIES, COLLABORATION
35
Core Data to Obtain for Data Sharing,
35
The FDA’s Critical Path Initiative,
37
A Proposal for the FDA’s Critical Path Initiative Under Development for Suicidality,
40
APPENDIXES
A
References
43
B
Workshop Agenda
51
C
Workshop Attendees
61
D
Biographical Sketches of Invited Speakers
65
