title: Phase I trials: from traditional to newer approaches. Part I.
abstract: Phase I clinical trials have traditionally been focused on populations of normal healthy volunteers with the goal of determining the safety, tolerability, and pharmacokinetic profile of new investigational agents. As CNS drug development shifts its focus to the development of novel molecular entities, this approach will undergo an evolution. In this first part of a two-part series, the authors describe the traditional Phase I approach as well as challenges facing CNS drug development. The second half of the series will propose modifications to the traditional phase I design, including the incorporation of different populations, bio-marker surrogates, and adaptive designs.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine-Wichita, KS, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Macaluso
authors.forename: Michael
authors.initials: M
authors.lastname: Krams
authors.forename: Sheldon H
authors.initials: SH
authors.lastname: Preskorn
mesh_terms: D026688:Bioethical Issues / Q000592:standards; D001711:Biotransformation; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects; D002491:Central Nervous System Agents / Q000737:chemistry / Q000493:pharmacokinetics; D017321:Clinical Trials, Phase I as Topic; D015195:Drug Design; D015507:Drugs, Investigational / Q000737:chemistry / Q000493:pharmacokinetics; D023381:Endpoint Determination / Q000379:methods / Q000592:standards; D006801:Humans; D033281:Nontherapeutic Human Experimentation / Q000941:ethics; D010597:Pharmacogenetics / Q000639:trends; D011619:Psychotropic Drugs / Q000737:chemistry / Q000493:pharmacokinetics; D012107:Research Design / Q000592:standards; D018581:Technology Transfer
chemical_list: D002491:Central Nervous System Agents; D015507:Drugs, Investigational; D011619:Psychotropic Drugs