title: Use of functional imaging across clinical phases in CNS drug development.
abstract: The use of novel brain biomarkers using nuclear magnetic resonance imaging holds potential of making central nervous system (CNS) drug development more efficient. By evaluating changes in brain function in the disease state or drug effects on brain function, the technology opens up the possibility of obtaining objective data on drug effects in the living awake brain. By providing objective data, imaging may improve the probability of success of identifying useful drugs to treat CNS diseases across all clinical phases (I-IV) of drug development. The evolution of functional imaging and the promise it holds to contribute to drug development will require the development of standards (including good imaging practice), but, if well integrated into drug development, functional imaging can define markers of CNS penetration, drug dosing and target engagement (even for drugs that are not amenable to positron emission tomography imaging) in phase I; differentiate objective measures of efficacy and side effects and responders vs non-responders in phase II, evaluate differences between placebo and drug in phase III trials and provide insights into disease modification in phase IV trials.
authors.affiliation: Center for Pain and the Brain, MGH, Children's and Mclean Hospitals, Harvard Medical School, Boston, MA, USA. david.borsook@childrens.harvard.edu
authors.forename: D
authors.initials: D
authors.lastname: Borsook
authors.forename: L
authors.initials: L
authors.lastname: Becerra
authors.forename: M
authors.initials: M
authors.lastname: Fava
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002493:Central Nervous System Diseases / Q000188:drug therapy; D017321:Clinical Trials, Phase I as Topic / Q000379:methods; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D059907:Functional Neuroimaging / Q000191:economics / Q000379:methods / Q000592:standards; D006801:Humans
chemical_list: D015415:Biomarkers; D002491:Central Nervous System Agents