title: Issues and perspectives in designing clinical trials for negative symptoms in schizophrenia.
abstract: A number of pharmacological agents for treating negative symptoms in schizophrenia are currently in development. Unresolved questions regarding the design of clinical trials in this area were discussed at an international meeting in Florence, Italy in April 2012. Participants included representatives from academia, the pharmaceutical industry, and the European Medicines Agency (EMA). Prior to the meeting, participants submitted key questions for debate and discussion. Responses to the questions guided the discussion during the meeting. The group reached agreement on a number of issues: (1) study subjects should be under the age of 65; (2) subjects should be excluded for symptoms of depression that do not overlap with negative symptoms; (3) functional measures should not be required as a co-primary in negative symptom trials; (4) information from informants should be included for ratings when available; (5) Phase 2 negative symptom trials should be 12weeks and 26weeks is preferred for Phase 3 trials; (6) prior to entry into a negative symptom study, subjects should demonstrate clinical stability for a period of 4 to 6months by collection of retrospective information; and (7) prior to entry, the stability of negative and positive symptoms should be confirmed prospectively for four weeks or longer. The participants could not reach agreement on whether predominant or prominent negative symptoms should be required for study subjects.
authors.affiliation: Semel Institute for Neuroscience at UCLA, Los Angeles, CA, USA; VA Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, CA, USA. Electronic address: marder@ucla.edu.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
authors.forename: Larry
authors.initials: L
authors.lastname: Alphs
authors.forename: Ion-George
authors.initials: IG
authors.lastname: Anghelescu
authors.forename: Celso
authors.initials: C
authors.lastname: Arango
authors.forename: Thomas R E
authors.initials: TR
authors.lastname: Barnes
authors.forename: Ivo
authors.initials: I
authors.lastname: Caers
authors.forename: David G
authors.initials: DG
authors.lastname: Daniel
authors.forename: Eduardo
authors.initials: E
authors.lastname: Dunayevich
authors.forename: W Wolfgang
authors.initials: WW
authors.lastname: Fleischhacker
authors.forename: George
authors.initials: G
authors.lastname: Garibaldi
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.forename: Philip D
authors.initials: PD
authors.lastname: Harvey
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.forename: Richard S E
authors.initials: RS
authors.lastname: Keefe
authors.forename: Bruce
authors.initials: B
authors.lastname: Kinon
authors.forename: Stefan
authors.initials: S
authors.lastname: Leucht
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lindenmayer
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.forename: Virginia
authors.initials: V
authors.lastname: Stauffer
authors.forename: Daniel
authors.initials: D
authors.lastname: Umbricht
authors.forename: Keith
authors.initials: K
authors.lastname: Wesnes
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rabinowitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents
keywords: Apathy; Negative symptoms; Schizophrenia