Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders: Proceedings of a Workshop

Compared With Other Disease Areas, Central Nervous System (cns) Disorders Have Had The Highest Failure Rate For New Compounds In Advanced Clinical Trials. Most Cns Drugs Fail Because Of Efficacy, And The Core Issue Underlying These Problems Is A Poor Understanding Of Disease Biology. Concern About The Poor Productivity In Neuroscience Drug Development Has Gained Intensity Over The Past Decade, Amplified By A Retraction In Investment From The Pharmaceutical Industry. This Retreat By Industry Has Been Fueled By The High Failure Rate Of Compounds In Advanced Clinical Trials For Nervous System Disorders. In Response To The De-emphasis Of Cns Disorders In Therapeutic Development Relative To Other Disease Areas Such As Cancer, Metabolism, And Autoimmunity, The National Academies Of Sciences, Engineering, And Medicine Initiated A Series Of Workshops In 2012 To Address The Challenges That Have Slowed Drug Development For Nervous System Disorders. Motivated By The Notion That Advances In Genetics And Other New Technologies Are Beginning To Bring Forth New Molecular Targets And Identify New Biomarkers, The Academies Hosted The Third Workshop In This Series In September 2016. Participants Discussed Opportunities To Accelerate Early Stages Of Drug Development For Nervous System Disorders In The Absence Of Animal Models That Reflect Disease And Predict Efficacy. This Publication Summarizes The Presentations And Discussions From The Workshop. Introduction And Overview -- Drug Development For Nervous System Disorders: Overview Of Challenges Adn Potential Opportunities -- Case Studies: Therapeutic Development For Parkinson's Disease And Schizophrenia In The Absence Of Predictive Animal Models Of Disease -- New Modeling Approaches For Nervous System Disorders -- Private-sector Thresholds For Investment In Neuroscience Clinical Trials -- Ethical Considerations -- Regulatory Perspectives -- Appendix A: References -- Appendix B: Workshop Agenda -- Appendix C: Registered Attendees. Lisa Bain, Sheena M. Posey Norris, Noam I. Keren, And Clare Stroud, Rapporteurs ; Forum On Neuroscience And Nervous System Disorders, Board On Health Sciences Policy, Health And Medicine Division, The National Academies Of Sciences, Engineering, Medicine. A Report Of The National Academies Of Sciences, Engineering, Medicine. Includes Bibliographical References. 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-c-0057); 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 Do Not Necessarily Reflect The Views Of Any Organization Or Agency That Provided Support For This Project.