THE NATIONAL ACADEMIES PRESS Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop Lisa Bain, Noam I Keren, and Clare Stroud, Rapporteurs Forum on Neuroscience and Nervous System Disorders Board on Health Sciences Policy Health and Medicine Division Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop THE NATIONAL ACADEMIES PRESS • 500 Fifth Street, NW • Washington, DC 20001 This project was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; Brain Canada Foundation; Cohen Veterans Bioscience; the Department of Health and Human Services’ Food and Drug Administration (5R13FD005362-02) and National Institutes of Health (NIH) (HHSN26300089 [Under Master Base # DHHS-10002880]) through the National Center for Complementary and Integrative Health, National Eye Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, and NIH Blueprint for Neuroscience Research; Department of Veterans Affairs (VA240-14-C0057); Eli Lilly and Company; Foundation for the National Institutes of Health; Gatsby Charitable Foundation; Janssen Research & Development, LLC; Lundbeck Research USA; Merck Research Laboratories; The Michael J Fox Foundation for Parkinson’s Research; National Multiple Sclerosis Society; National Science Foundation (BCS-1064270); One Mind; Pfizer Inc.; Pharmaceutical Product Development, LLC; Sanofi; Society for Neuroscience; and Takeda Development Center Americas, Inc Any opinions, findings, conclusions, or recommendations expressed in this publication not necessarily reflect the views of any organization or agency that provided support for this project International Standard Book Number-13: 978-0-309-45026-3 International Standard Book Number-10: 0-309-45026-8 Digital Object Identifier: 10.17226/23657 Additional copies of this publication are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu Copyright 2017 by the National Academy of Sciences All rights reserved Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine 2017 Developing multimodal therapies for brain disorders: Proceedings of a workshop Washington, DC: The National Academies Press doi: 10.17226/23657 Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop The National N Aca ademy of Sciences was established in 1863 by an Actt of Congresss, signed byy President LLincoln, as a private, nongo overnmentall institution to advise th he nation on n issues relate ed to science e and techno ology Memb bers are ele ected by their peers for outstand ding contribu utions to ressearch Dr M Marcia McNu utt is president N Aca ademy of En ngineering w was establish hed in 1964 The National underr the charterr of the Natiional Academ my of Sciencces to bring the prractices of engineering e to advising tthe nation Members arre electe ed by their peers p for exttraordinary contribution ns to engine eering Dr C C D Mote, Jr., is presid dent merly the In The National N Aca ademy of Me edicine (form nstitute of Medic cine) was esttablished in 1970 underr the charterr of the Nation nal Academyy of Science es to advise tthe nation o on medical and he ealth issues Members are a elected by their pee ers for distinguished contributions to o medicine aand health Dr Victor JJ i president Dzau is he Nationall Academiess The th hree Academ mies work to ogether as th of Sciences, Engiineering, an nd Medicine e to provide independent, objective analyysis and adv ice to the nation and uct other acttivities to so olve complexx problems and inform condu public c policy deciisions The National N Acaademies also o encourage e educa ation and ressearch, reco ognize outstaanding conttributions to knowlledge, and increase pub blic understaanding in ma atters of scienc ce, engineerring, and me edicine es, Learn more aboutt the Nation nal Academie es of Science Engine eering, and Medicine att www.natio onal-academ mies.org Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop Reporrts documen nt the evidence-based cconsensus off an authorin ng comm mittee of exp perts Reporrts typically include find dings, conclu usions, and recommendations based d on informa ation gathered by the committee c and a committtee delibera ations nd are appro oved by the National Reporrts are peer reviewed an Acade emies of Scie ences, Engin neering, and d Medicine Proce eedings chro onicle the prresentationss and discusssions at a worksshop, symposium, or oth her convenin ng event Th he statemen nts and opinions conttained in pro oceedings arre those of tthe cipants and have h not bee en endorsed d by other participants, partic the pllanning committee, or the t Nationall Academies of Sciencess, Engine eering, and Medicine For information about a other products an d activities of the Nation nal Academiies, please visit v nation nalacademie es.org/whatw wedo Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop PLANNING COMMITTEE ON MULTIMODAL THERAPIES FOR BRAIN DISORDERS1 KARL KIEBURTZ (Co-Chair), University of Rochester Medical Center SARAH H LISANBY (Co-Chair), National Institute of Mental Health ROBERT ALEXANDER, Pfizer Inc TIM DENISON, Medtronic Inc JAMES HENDRIX, Alzheimer’s Association THINH NGUYEN, Food and Drug Administration DAVID SHURTLEFF, National Center for Complementary and Integrative Health TIMOTHY STRAUMAN, Duke University STEVIN ZORN, MindImmune Therapeutics, Inc Health and Medicine Division (HMD) Staff CLARE STROUD, Forum Director SHEENA M POSEY NORRIS, Program Officer NOAM I KEREN, Associate Program Officer (from June 2016) JOANNA ROBERTS, Senior Program Assistant (until April 2016) ANDREW M POPE, Director, Board on Health Sciences Policy The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution v Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS1 STEVEN HYMAN (Chair), Broad Institute of Massachusetts Institute of Technology and Harvard University STORY LANDIS (Vice Chair), Director Emeritus, National Institute of Neurological Disorders and Stroke SUSAN AMARA, Society for Neuroscience RITA BALICE-GORDON, Sanofi KATJA BROSE, Cell Press EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology DANIEL BURCH, Pharmaceutical Product Development, LLC SARAH CADDICK, Gatsby Charitable Foundation ROSA CANET-AVILES, Foundation for the National Institutes of Health MARIA CARRILLO, Alzheimer’s Association KAREN CHANDROSS, Sanofi (until June 2016) E ANTONIO CHIOCCA, Harvard Medical School TIMOTHY COETZEE, National Multiple Sclerosis Society JONATHAN COHEN, Princeton University FAY LOMAX COOK, National Science Foundation BRUCE CUTHBERT, National Institute of Mental Health (until September 2016) BILLY DUNN, Food and Drug Administration EMMELINE EDWARDS, National Center for Complementary and Integrative Health (until September 2016) JOSHUA GORDON, National Institute of Mental Health (from September 2016) HANK GREELY, Stanford University RAQUEL GUR, University of Pennsylvania MAGALI HAAS, Cohen Veterans Bioscience RAMONA HICKS, One Mind RICHARD HODES, National Institute on Aging STUART HOFFMAN, U.S Department of Veterans Affairs MICHAEL IRIZARRY, Eli Lilly and Company The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables not issue, review, or approve individual documents The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution vii Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop INEZ JABALPURWALA, Brain Canada Foundation FRANCES JENSEN, University of Pennsylvania GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke ALAN LESHNER, American Association for the Advancement of Science (Emeritus) HUSSEINI MANJI, Janssen Research & Development, LLC DAVID MICHELSON, Merck Research Laboratories PATRICIO O’DONNELL, Pfizer Inc JAMES OLDS, National Science Foundation ATUL PANDE, Tal Medical STEVEN PAUL, Voyager Therapeutics, Inc RODERIC PETTIGREW, National Institute of Biomedical Imaging and Bioengineering (from September 2016) EMILIANGELO RATTI, Takeda Pharmaceuticals International TODD SHERER, The Michael J Fox Foundation for Parkinson’s Research DAVID SHURTLEFF, National Center for Complementary and Integrative Health PAUL SIEVING, National Eye Institute NORA VOLKOW, National Institute on Drug Abuse STEVIN ZORN, MindImmune Therapeutics, Inc HMD Staff CLARE STROUD, Forum Director SHEENA M POSEY NORRIS, Program Officer NOAM I KEREN, Associate Program Officer (from June 2016) JOANNA ROBERTS, Senior Program Assistant (until April 2016) DANIEL FLYNN, Senior Program Assistant (from September 2016) JIM BANIHASHEMI, Financial Officer HILARY BRAGG, Program Coordinator ANDREW M POPE, Director, Board on Health Sciences Policy viii Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop Reviewers This Proceedings of a Workshop has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published Proceedings of a Workshop as sound as possible and to ensure that the Proceedings of a Workshop 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 Proceedings of a Workshop: BRUCE BEBO, National Multiple Sclerosis Society BRIAN FISKE, The Michael J Fox Foundation for Parkinson’s Research KEITH HILDEBRAND, Medtronic, Inc ROGER J LEWIS, David Geffen School of Medicine at UCLA HELEN S MAYBERG, Emory University School of Medicine Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the Proceedings of a Workshop before its release The review of this Proceedings of a Workshop was overseen by JOSEPH T COYLE, Harvard Medical School He was responsible for making certain that an independent examination of this Proceedings of a Workshop was carried out in accordance with institutional procedures and that all review comments were carefully considered Responsibility for the final content of this Proceedings of a Workshop rests entirely with the rapporteurs and the institution ix Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 70 MULTIMODAL THERAPIES FOR BRAIN DISORDERS 2:00 p.m Part A: Two Pharmacological Interventions Approved as a Co-Delivery Drug/Drug and Drug/Biologic Combinations for Alzheimer’s Disease JAMES HENDRIX Director, Global Science Initiatives, Medical and Scientific Relations Alzheimer’s Association 2:10 p.m Part B: Concomitant Prescription of Two Interventions with Different Modalities Drug−Device Combinations for Epilepsy MARTHA MORRELL Chief Medical Officer, NeuroPace Clinical Professor of Neurology and, by courtesy, Neurosurgery Stanford University Combining Drugs and Psychosocial Interventions in Adolescents with Bipolar Disorder KIKI CHANG (via WebEx) Professor of Psychiatry and Behavioral Sciences Stanford University Medical Center 2:30 p.m Part C: Simultaneous Use of Two Modalities in a Single Procedure Combining Devices with Cognitive Enhancement BRUCE LUBER Staff Scientist Experimental Therapeutics & Pathophysiology Branch National Institute of Mental Health Individually Targeted Combination of Transcranial Magnetic Stimulation and a Psychosocial Intervention TIMOTHY STRAUMAN Professor of Psychology and Neuroscience Duke University 2:50 p.m Discussion Among Speakers and Workshop Participants 3:30 p.m BREAK Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 71 APPENDIX B SESSION II: REGULATORY AND REIMBURSEMENT CONSIDERATIONS Session Objectives: • Consider regulatory and reimbursement issues for multimodal therapies, including for approaches in which two components are regulated (e.g., drug plus device) and approaches in which only one component is regulated (e.g., drug plus psychosocial intervention) • Explore evidentiary standards needed for regulation and reimbursement, and consider how different approval pathways and evidentiary standards across FDA centers impact multimodal approaches • Discuss potential opportunities for addressing challenges 3:45 p.m Session Overview and Objectives SARAH H LISANBY, Session Moderator Director, Division of Translational Research National Institute of Mental Health 3:55 p.m Part A: Regulatory Considerations Combination Products at the Food and Drug Administration PATRICIA LOVE Deputy Director, Office of Combination Products Food and Drug Administration Evaluating Multimodal Products at the Center for Drug Evaluation and Research BILLY DUNN Director, Division of Neurology Products Office of Drug Evaluation I Center for Drug Evaluation and Research Food and Drug Administration Evaluating Multimodal Products at the Center for Devices and Radiological Health CARLOS PEÑA Director, Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health Food and Drug Administration Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 72 MULTIMODAL THERAPIES FOR BRAIN DISORDERS Evaluating Multimodal Products at the Center for Biologics Evaluation and Research WILSON BRYAN Director, Division of Clinical Evaluation & Pharmacology/Toxicology Office of Cellular, Tissue, and Gene Therapies Center for Biologics Evaluation and Research Food and Drug Administration 4:35 p.m Part B: Payer Considerations Private Payer Considerations RHONDA ROBINSON-BEALE Senior Vice President and Chief Medical Officer Blue Cross of Idaho Perspectives from a Government Payer STEVEN PIZER Associate Professor of Health Economics Department of Pharmacy and Health Systems Sciences Northeastern University and Chief Economist, Health Care Financing & Economics U.S Department of Veterans Affairs 4:55 p.m Discussion Among Speakers and Workshop Participants 5:30 p.m Adjourn Day One Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 73 APPENDIX B DAY TWO: June 15, 2016 8:30 a.m Day Two Opening Remarks KARL KIEBURTZ, Workshop Co-Chair SARAH H LISANBY, Workshop Co-Chair KEYNOTE TALK: FUTURE DIRECTIONS IN CLINICAL TRIALS AND REGULATORY APPROACHES FOR MULTIMODAL THERAPIES 8:40 a.m ROBERT CALIFF Commissioner of Food and Drugs Food and Drug Administration 9:00 a.m Questions and Answers with Workshop Participants 9:30 a.m BREAK SESSION III: ESTABLISHING EFFICACY AND SAFETY IN MULTIMODAL THERAPIES FOR BRAIN DISORDERS Session Objectives: Discuss methodologies for establishing efficacy and safety for multimodal therapies compared to monotherapies, including clinical and statistical considerations Potential topics may include • • • • Addressing challenges of intervention fidelity (e.g., site-tosite and time-to-time consistency) with behavioral interventions (psychotherapy, exercise); Interpretation when the two modalities have different time courses (e.g., drug goes for longer than behavioral intervention); Interpretation when one modality encounters more intolerability; Different approaches to assessing dose, especially in psychosocial interventions; or Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 74 MULTIMODAL THERAPIES FOR BRAIN DISORDERS • Innovative approaches to trial design that are specifically relevant to multimodal approaches and may help address the levels of evidence required for regulation and reimbursement 9:45 a.m Session Overview and Objectives KARL KIEBURTZ, Session Moderator Robert J Joynt Professor in Neurology Senior Associate Dean for Clinical Research Director of the Clinical & Translational Science Institute University of Rochester Medical Center 9:55 a.m Platform Trials for Multimodal Therapies ROGER LEWIS Senior Medical Scientist, Berry Consultants Professor and Chair, Department of Emergency Medicine, Harbor-UCLA Medical Center Quantification of Dose with Devices MAROM BIKSON Professor of Biomedical Engineering The City College of the City University of New York Quantification of Dose in Psychosocial Interventions WOLFGANG LUTZ (via WebEx) Professor and Head of Clinical Psychology and Psychotherapy University of Trier, Germany 10:45 a.m Discussants: BILLY DUNN Director, Division of Neurology Products Office of Drug Evaluation I Center for Drug Evaluation and Research Food and Drug Administration RHONDA ROBINSON-BEALE Senior Vice President and Chief Medical Officer Blue Cross of Idaho Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 75 APPENDIX B STEVEN PIZER Associate Professor of Health Economics Department of Pharmacy and Health Systems Sciences Northeastern University and Chief Economist, Health Care Financing & Economics U.S Department of Veterans Affairs 11:15 a.m Discussion Among Speakers, Discussants, and Workshop Participants 11:45 a.m LUNCH SESSION IV: INDUSTRY PERSPECTIVES Session Objectives: • Discuss industry perspectives on particular technical, scientific, and commercial challenges to bringing these systems to market, and examine lessons learned from successful examples of collaborations on multimodal approaches • Explore potential mechanisms for addressing challenges and enabling multimodal therapy development programs 12:30 p.m 12:40 p.m Session Overview and Objectives STEVIN ZORN, Session Moderator Executive Scientist in Residence Lundbeck Challenges and Opportunities for Integration of Therapeutic Devices into Psychiatry JEFFREY NYE Vice President, Neuroscience Innovation and Scientific Partnership Strategy Janssen Research and Development, LLC Johnson & Johnson Innovation Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 76 MULTIMODAL THERAPIES FOR BRAIN DISORDERS Intrathecal Infusion Therapy for Chronic Pain: Challenges, Lessons, and Opportunities KEITH HILDEBRAND Senior Principal Scientist, Technical Fellow Neuromodulation Medtronic, Inc Pfizer–MedGenesis Therapeutix Collaboration on Glial Cell Line-Derived Neurotrophic Factor (GDNF) Protein and Convection Enhanced Delivery (CED) Technology for Parkinson’s Disease ERICH MOHR Chair & Chief Executive Officer MedGenesis Therapeutix Inc CHRISTOPHER SHAFFER Associate Research Fellow Pfizer Inc 1:20 p.m Discussion Among Speakers and Workshop Participants 2:00 p.m BREAK SESSION V: MOVING FORWARD Session Objectives: • Discuss the roles of NIH, other research agencies, and diseasespecific organizations in supporting the development of multimodal therapies • Synthesize and discuss key highlights from the workshop presentations and discussions and, most importantly, identify next steps and promising areas for future action and research 2:15 p.m Session Overview and Objectives KARL KIEBURTZ, Workshop Co-Chair and Session Moderator SARAH H LISANBY, Workshop Co-Chair and Session Moderator Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 77 APPENDIX B 2:20 p.m Role of Research Agencies in De-Risking Multimodal Therapy Development AMIR TAMIZ Program Director, NIH Blueprint NeuroTherapeutics Network National Institutes of Health STUART HOFFMAN Senior Scientific Advisor for Brain Injury Office of Research and Development Department of Veterans Affairs 2:40 p.m Role of Disease-Specific Research Funding in Multimodal Therapy Development JAMES HENDRIX Director, Global Science Initiatives, Medical and Scientific Relations Alzheimer’s Association BRIAN FISKE Senior Vice President, Research Programs The Michael J Fox Foundation for Parkinson’s Research 3:00 p.m Discussion with Workshop Participants 3:15 p.m Panel Discussion: Identifying Gaps, Opportunities, and Next Steps Highlighted in Workshop Presentations and Discussions KARL KIEBURTZ, Workshop Co-Chair and Session III Moderator SARAH H LISANBY, Workshop Co-Chair and Session II Moderator KEITH HILDEBRAND, Session I Co-Moderator TIMOTHY STRAUMAN, Session I Co-Moderator STEVIN ZORN, Session IV Moderator EMMELINE EDWARDS Director, Division of Extramural Research National Center for Complementary and Integrative Health Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 78 MULTIMODAL THERAPIES FOR BRAIN DISORDERS 4:00 p.m Discussion with Workshop Participants 4:20 p.m Closing Remarks KARL KIEBURTZ, Workshop Co-Chair SARAH H LISANBY, Workshop Co-Chair 4:30 p.m Adjourn Workshop Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop C Registered Participants Neeraj Agarwal National Eye Institute Kristopher Bough National Institute on Drug Abuse Seun Ajiboye Johns Hopkins Medical Institution Linda Brady National Institute of Mental Health Irina Antonijevic Sanofi Jeremy Brown National Institute of General Medical Sciences Shelli Avenevoli National Institute of Mental Health Wilson Bryan Food and Drug Administration Rita Balice-Gordon Sanofi Sonia Bansal George Mason University Ethan Buch National Institute of Neurological Disorders and Stroke Marom Bikson The City College of the City University of New York Sarah Caddick The Gatsby Charitable Foundation Chris Boshoff National Institute of Neurological Disorders and Stroke Robert Califf Food and Drug Administration 79 Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 80 MULTIMODAL THERAPIES FOR BRAIN DISORDERS Maria Carrillo Alzheimer’s Association Karen Chandross Sanofi Emmeline Edwards National Center for Complementary and Integrative Health Kiki Chang Stanford University Medical Center Rebecca English National Academies of Sciences, Engineering, and Medicine Timothy Coetzee National Multiple Sclerosis Society Jennifer Evans National Institute of Mental Health Richard Conroy National Institute of Biomedical Imaging and Bioengineering Jovier Evans National Institute of Mental Health Nathaniel Counts Mental Health America Brian Fiske The Michael J Fox Foundation for Parkinson’s Research Bruce Cuthbert National Institute of Mental Health Mads Dalsgaard Lundbeck Ann Marie D’Angelo Family Care Connections, LLC James Deshler National Science Foundation Sonya Dumanis Milken Institute Billy Dunn Food and Drug Administration Naz Ghassemian Food and Drug Administration Theresa Gleason U.S Department of Veterans Affairs Alex Goddard Tal Medical Anupama Govindarajan Food and Drug Administration Hank Greely Stanford University Laura Helbling The RPM Report Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 81 APPENDIX C James Hendrix Alzheimer’s Association Ramona Hicks One Mind Keith Hildebrand Medtronic, Inc J Terrell Hoffeld U.S Public Health Service (Retired) Stuart Hoffman U.S Department of Veterans Affairs Euchay Horsman University of Arkansas at Little Rock Steven Hyman Broad Institute of Massachusetts Institute of Technology and Harvard University Debbie Indyk Icahn School of Medicine at Mount Sinai Michael Irizarry Eli Lilly and Company Inez Jabalpurwala Brain Canada Foundation John Johnson Physical Rehabilitation Inc Claire Kaplan University of Maryland, College Park Morris Kaplan Food and Drug Administration John Kehne National Institute of Neurological Disorders and Stroke Karl Kieburtz University of Rochester Medical Center Walter Koroshetz National Institute of Neurological Disorders and Stroke Judith Lelchook Solace Center Alan Leshner American Association for the Advancement of Science Laura Levit American Society of Clinical Oncology Roger Lewis Harbor-UCLA Medical Center Sarah H Lisanby National Institute of Mental Health Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 82 MULTIMODAL THERAPIES FOR BRAIN DISORDERS Leonid Livshitz Food and Drug Administration Patricia Love Food and Drug Administration Ying Lu U.S Department of Veterans Affairs Bruce Luber National Institute of Mental Health Wolfgang Lutz University of Trier Erich Mohr MedGenesis Martha J Morrell NeuroPace Joan Murray Murray Enterprises Lawrence Park National Institute of Mental Health Mary Pelleymounter National Institute of Neurological Disorders and Stroke Carlos Peña Food and Drug Administration Linda M Picon U.S Department of Veterans Affairs Steven Pizer Northeastern University/Veteran Affairs Boston Health Care System William Potter National Institute of Mental Health Venkatesha Murthy Takeda Thomas Radman National Institute on Drug Abuse Jeffrey Nye Johnson & Johnson Innovation Vesper Ramos Food and Drug Administration Robert O’Brien U.S Department of Veterans Affairs John Reppas Neurotechnology Industry Organization Gerald Overman National Institute of Mental Health Rhonda Robinson-Beale Blue Cross of Idaho Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop 83 APPENDIX C Judith Rumsey National Institute of Mental Health Paul Wilburn U.S Department of Justice (Retired) Alexander Runko U.S Department of Health and Human Services Alex Wong Washington University School of Medicine Aminata Sallah Consultant Ling Wong National Institute of Neurological Disorders and Stroke Betty Jo Salmeron National Institute on Drug Abuse Joel Scholten U.S Department of Veterans Affairs Christopher Shaffer Pfizer Inc Daniel Stevenson Walter Reed Army Institute of Research Winifred Wu Strategic Regulatory Partners, LLC Farid Yaghouby Food and Drug Administration Danna Zimmer University of Maryland School of Medicine Stevin Zorn MindImmune Therapeutics, Inc Timothy Strauman Duke University Domenica Tambasco University of Toronto Amir Tamiz National Institute of Neurological Disorders and Stroke Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop Copyright © National Academy of Sciences All rights reserved ... rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop MULTIMODAL THERAPIES FOR BRAIN DISORDERS RATIONALE FOR MULTIMODAL THERAPIES IN BRAIN DISORDERS Several... Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop MULTIMODAL THERAPIES FOR BRAIN DISORDERS forward In Chapter 3, the state of the... reserved Developing Multimodal Therapies for Brain Disorders: Proceedings of a Workshop Copyright © National Academy of Sciences All rights reserved Developing Multimodal Therapies for Brain Disorders: