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In the Circuit Court 1 1 FOOD AND DRUG ADMINISTRATION 2 CENTER FOR DRUG EVALUATION AND RESEARCH 3 4 5 6 JOINT MEETING OF THE PSYCHOPHARMACOLOGIC DRUGS AND 7 DRUG AND RISK MANAGEMENT ADVISORY COMMITTEES 8 (PDAC and DSaRM) 9 10 11 12 13 Thursday, November 1, 2018 14 8:00 a.m. to 5:01 p.m. 15 16 17 18 19 FDA White Oak Campus 20 Building 31, the Great Room 21 10903 New Hampshire Avenue 22 Silver Spring, Maryland A Matter of Record (301) 890-4188 2 1 Meeting Roster 2 DESIGNATED FEDERAL OFFICER (Non-Voting) 3 Kalyani Bhatt, BS, MS 4 Division of Advisory Committee and Consultant 5 Management 6 Office of Executive Programs, CDER, FDA 7 PSYCHOPHARMACOLOGIC DRUGS ADVISORY COMMITTEE 8 MEMBERS (Voting) 9 10 Walter S. Dunn, MD, PhD 11 Staff Psychiatrist and Assistant Clinical Professor 12 West Los Angeles Veterans Administration Medical 13 Center 14 University of California Los Angeles 15 Department of Psychiatry 16 Los Angeles, California 17 18 19 20 21 22 A Matter of Record (301) 890-4188 3 1 Jess G. Fiedorowicz, MD, PhD 2 Associate Professor 3 Departments of Psychiatry, Epidemiology and 4 Internal Medicine 5 University of Iowa Carver College of Medicine 6 Iowa City, Iowa 7 8 Satish Iyengar, PhD 9 Chair and Professor of Statistics 10 Department of Statistics 11 University of Pittsburgh 12 Pittsburgh, Pennsylvania 13 14 Felipe A. Jain, MD 15 Assistant Clinical Professor of Psychiatry 16 Department of Psychiatry 17 University of California, San Francisco 18 401 Parnassus Avenue, Langley Porter 19 San Francisco, California 20 21 22 A Matter of Record (301) 890-4188 4 1 Rajesh Narendran, MD 2 (Chairperson) 3 Attending Psychiatrist 4 Re:solve Crisis Network 5 Western Psychiatric Institute and Clinics 6 Associate Professor in Radiology and Psychiatry 7 Psychiatric Molecular Imaging Program 8 University of Pittsburgh 9 Pittsburgh, Pennsylvania 10 11 Kim O. Wictzak 12 (Consumer Representative) 13 Co-Founder, Executive Director 14 Woodymatters 15 Minneapolis, Minnesota 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 5 1 PSYCHOPHARMACOLOGIC DRUGS ADVISORY COMMITTEE MEMBER 2 (Non-Voting) 3 Robert R. Conley, MD 4 (Industry Representative) 5 Global Development Leader 6 Pain and Core Therapeutic 7 Team and Distinguished Scholar 8 Eli Lilly and Company 9 Lilly Corporate Center 10 Indianapolis, Indiana 11 12 DRUG SAFETY AND RISK MANAGEMENT ADVISORY COMMITTEE 13 MEMBERS (Voting) 14 Kelly Besco, PharmD, FISMP, CPPS 15 Health-System Medication Safety Officer 16 OhioHealth Pharmacy Services 17 Dublin, Ohio 18 19 20 21 22 A Matter of Record (301) 890-4188 6 1 Marie R. Griffin, MD, MPH 2 Professor, Health Policy and Medicine 3 Director, Vanderbilt MPH Program 4 Department of Health Policy 5 Vanderbilt University Medical Center 6 Nashville, Tennessee 7 8 Laurel A. Habel, MPH, PhD 9 Associate Director, Cancer Research 10 Division of Research 11 Kaiser Permanente Northern California 12 Oakland, California 13 14 Sonia Hernandez-Diaz, MD, MPH, DrPH 15 Professor of Epidemiology 16 Department of Epidemiology 17 Harvard T.H. Chan School of Public Health 18 Boston, Massachusetts 19 20 21 22 A Matter of Record (301) 890-4188 7 1 Martin Kulldorff, PhD 2 Professor of Medicine and Biostatistician 3 Division of Pharmacoepidemiology and 4 Pharmacoeconomics 5 Department of Medicine 6 Harvard Medical School and Brigham & Women's 7 Hospital 8 Boston, Massachusetts 9 10 Steven B. Meisel, PharmD 11 System Director of Patient Safety 12 Fairview Health Services 13 Minneapolis, Minnesota 14 15 Anne-Michelle Ruha, MD, FACMT 16 Director, Medical Toxicology Fellowship Program 17 Department of Medical Toxicology 18 Banner University Medical Center 19 Clinical Associate Professor of Emergency Medicine 20 University of Arizona College of Medicine 21 Phoenix, Arizona 22 A Matter of Record (301) 890-4188 8 1 Terri L. Warholak, PhD, RPh, CPHQ, FAPhA 2 Professor and Assistant Dean 3 Academic Affairs and Assessment 4 College of Pharmacy 5 University of Arizona 6 Tucson, Arizona 7 8 TEMPORARY MEMBERS (Voting) 9 Jane B. Acri, PhD 10 Chief, Medication Discovery & Toxicology 11 Branch 12 Division of Therapeutics and Medical 13 Consequences 14 National Institute on Drug Abuse 15 National Institutes of Health (NIH) 16 Bethesda, Maryland 17 18 19 20 21 22 A Matter of Record (301) 890-4188 9 1 David Cella, PhD 2 Professor Chairperson 3 Medical Social Sciences 4 Northwestern University Feinberg School of 5 Medicine 6 Chicago, Illinois 7 8 Stephanie Y. Crawford, PhD, MPH 9 Department of Pharmacy Systems 10 Outcomes and Policy 11 University of Chicago 12 Chicago, Illinois 13 14 Harriet de Wit, PhD 15 Department of Psychiatry and Behavioral 16 Neuroscience 17 The University of Chicago 18 Chicago, Illinois 19 20 21 22 A Matter of Record (301) 890-4188 10 1 Kathryn E. Flynn, PhD 2 Associate Professor of Medicine 3 Division of Hematology and Oncology 4 Senior Scientific Director for Patient-Reported 5 Outcomes 6 Center for International Blood & Marrow Transplant 7 Research 8 Milwaukee, Wisconsin 9 10 Roxanne E. Jensen, PhD 11 Program Director 12 Outcomes Research Branch 13 Health Care Delivery Research Program 14 Division of Cancer Control and Population Sciences 15 National Cancer Institute, NIH 16 Bethesda, Maryland 17 18 Elizabeth Joniak-Grant 19 (Patient Representative) 20 Holly Springs, North Carolina 21 22 A Matter of Record (301) 890-4188 11 1 Brandon D.L. Marshall, PhD 2 Associate Professor 3 Department of Epidemiology 4 Brown University School of Public Health 5 Providence, Rhode Island 6 7 William T. Riley, PhD 8 Director 9 Office of Behavioral and Social Sciences Research 10 NIH 11 Bethesda, Maryland 12 13 FDA PARTICIPANTS (Non-Voting) 14 Robert Temple, MD 15 Deputy Director for Clinical Science 16 CDER FDA 17 Deputy Director (Acting) 18 Office of Drug Evaluation I (ODE I) 19 Office of New Drugs (OND), CDER, FDA 20 21 22 A Matter of Record (301) 890-4188 12 1 Ellis Unger, MD 2 Director 3 ODE I, OND, CDER, FDA 4 5 Mitchell Mathis, MD 6 Division Director 7 Division of Psychiatry Products (DPP) 8 ODE I, OND, CDER, FDA 9 10 Judy Staffa, PhD, RPh 11 Associate Director for Public Health Initiatives 12 Division of Epidemiology II (DEPI-II) 13 Office of Pharmacovigilance and Epidemiology 14 Office of Surveillance and Epidemiology 15 CDER, FDA 16 17 Tiffany Farchione, MD 18 Deputy Director 19 DPP, ODE I, OND, CDER, FDA 20 21 22 A Matter of Record (301) 890-4188 13 1 Dominic Chiapperino, PhD 2 Director 3 Controlled Substance Staff 4 Office of the Center Director, CDER, FDA 5 6 Daniel J. Lee, MD 7 Clinical Reviewer 8 DPP, ODE I, OND, CDER, FDA 9 10 Semhar Ogbagaber, PhD 11 Statistician 12 Division of Biometrics I 13 Office of Biostatistics 14 Office of Translational Sciences, CDER, FDA 15 16 17 18 19 20 21 22 A Matter of Record (301) 890-4188 14 1 C O N T E N T S 2 AGENDA ITEM PAGE 3 Call to Order and Introduction of Committee 4 Raj Narendran, MD 17 5 Conflict of Interest Statement 6 Kalyani Bhatt, BS, MS 23 7 FDA Opening Remarks 8 Mitchell Mathis, MD 27 9 Applicant Presentations - Alkermes, Inc. 10 Introduction 11 Lisa von Moltke, MD 40 12 The Unmet Need in MDD and Challenges in 13 MDD Clinical Trials 14 George Papakostas, MD 51 15 Clinical Efficacy 16 Jerald Schindler, DrPH 65 17 Clinical Safety, and Risk Mitigation 18 Strategies 19 Gary Bloomgren, MD 97 20 21 22 A Matter of Record (301) 890-4188 15 1 C O N T E N T S (continued) 2 AGENDA ITEM PAGE 3 Clinical Perspective and Benefit-Risk 4 Profile 5 Sanjay Mathew, MD 116 6 Conclusion 7 Lisa von Moltke, MD 122 8 Clarifying Questions to Applicant 123 9 FDA Presentations 10 Regulatory History 11 Tiffany Farchione, MD 155 12 Clinical Efficacy and Safety Overview 13 Semhar Ogbagaber, PhD 166 14 Daniel Lee, MD 181 15 Abuse Potential of 16 Buprenorphine/Samidorphan (BUP/SAM) 17 Edward Hawkins, PhD 187 18 FDA Review of the Epidemiologic and 19 Surveillance Data 20 Celeste Mallama, PhD, MPH 197 21 22 A Matter of Record (301) 890-4188 16 1 C O N T E N T S (continued) 2 AGENDA ITEM PAGE 3 University of Washington Medical School 4 Department of Psychiatry and 5 Behavioral Sciences Presentation 6 Depression Effects on Long-Term 7 Prescription Opioid Use, Abuse and 8 Addiction 9 Mark Sullivan, MD, PhD 207 10 FDA Presentations (continued) 11 Risk Management for 12 Buprenorphine/Samidorphan 13 Somya Dunn, MD 221 14 Clarifying Questions to FDA and 228 15 Dr. Sullivan 16 Open Public Hearing 268 17 Clarifying Questions (continued) 332 18 Charge to the Committee 19 Mitchell Mathis, MD 335 20 Questions to the Committee and Discussion 336 21 Adjournment 446 22 A Matter of Record (301) 890-4188 17 1 P R O C E E D I N G S 2 (8:01 a.m.) 3 Call to Order 4 Introduction of Committee 5 DR. NARENDRAN: I would first like to remind 6 everyone to please silence your cell phones, 7 smartphones, other devices if you have not already 8 done so. I would also like to identify the FDA 9 press contact, Sandy Walsh. If you're there, 10 please stand. She's over there. 11 My name is Raj Narendran. I'm the 12 chairperson for today's meeting. I will now call 13 the Joint Meeting of the Psychopharmacology Drug 14 Advisory Committee and the Drug Safety and Risk 15 Management Advisory Committee to order. 16 We'll start by going around the table and 17 introduce ourselves.
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