title: Translational and Early Phase Strategies for Treatment Development: Report of ISCTM Autumn 2013 Symposium.
abstract: For decades, there has been a distinct disconnect translating a compound's effects from basic neuroscience into clinical efficacy. This disconnect has not only been in terms of generating approved compounds, but also in rejecting targets. During the drug discovery process there are key points to be adhered to that would strengthen the likelihood of a compound being translated to the clinic. These points include 1) the importance of translational pharmacology whereby preclinical pharmacological data should predict clinical efficacy; 2) rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3) using exposure response modeling to predict drug efficacy during proof-of-concept trials; 4) designing and conducting the appropriate proof-of-concept study; and 5) optimizing Phase II studies to set the stage for success in Phase III trials. These topics were covered in The International Society for CNS Clinical Trials and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and early development strategies and tools led by Drs. Potter and Feltner. This report comprises a review of those proceedings with a concluding summary to advance future clinical trials.
authors.affiliation: Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Young
authors.affiliation: Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
authors.forename: William Z
authors.initials: WZ
authors.lastname: Potter
authors.affiliation: Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
authors.forename: Steve
authors.initials: S
authors.lastname: Riley
authors.affiliation: Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Groeneveld
authors.affiliation: Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Kinon
authors.affiliation: Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
authors.forename: Mike F
authors.initials: MF
authors.lastname: Egan
authors.affiliation: Dr. Young is with the Department of Psychiatry, University of California San Diego, La Jolla, California, and Research Service, VA San Diego Healthcare System, San Diego, California; Dr. Potter is with the National Institute of Mental Health, Rockville, Maryland; Dr. Riley is with the Department of Clinical Pharmacology, Global Innovative Pharma Business, Pfizer, Inc., Groton, Connecticut; Dr. Groeneveld is with Center for Human Drug Research, The Netherlands; Dr. Kinon is with Lundbeck LLC, Deerfield, Illinois (Dr. Kinon was with Eli Lilly and Company, Indianapolis, Indiana, when this material was presented); Dr. Egan is with Clinical Neuroscience, Merck & Co, Inc, North Wales, Pennsylvania; and Dr. Feltner is with AbbVie Inc. Pharmaceuticals, Chicago, Illinois.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Feltner
keywords: Drug discovery; FDA; decision-making; pharmacokinetics; pharmacology; proof of concept; target rejection