title: Functional co-primary measures for clinical trials in schizophrenia: results from the MATRICS Psychometric and Standardization Study.
abstract: OBJECTIVE
  During the consensus meetings of the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS) Initiative, the U.S. Food and Drug Administration took the position that a drug for this purpose should show changes on 1) an accepted consensus cognitive performance measure and 2) an additional measure (i.e., a co-primary) that is considered functionally meaningful. The goal of the current study was to describe steps to evaluate four potential co-primary measures for psychometric properties and validity.
  
  
  METHODS
  As part of the five-site MATRICS Psychometric and Standardization Study (PASS), two measures of functional capacity and two interview-based measures of cognition were evaluated in 176 patients with schizophrenia (167 of these patients were retested 4 weeks later).
  
  
  RESULTS
  Data are presented for each co-primary measure for test-retest reliability, utility as a repeated measure, relationship to cognitive performance, relationship to functioning, tolerability/practicality, and number of missing data.
  
  
  CONCLUSIONS
  Psychometric properties of all of the measures were considered acceptable, and the measures were generally comparable across the various criteria, except that the functional capacity measures had stronger relationships to cognitive performance and fewer missing data. The development and evaluation of potential co-primary measures is still at an early stage, and it was decided not to endorse a single measure for clinical trials at this point. The current findings offer the initial steps to identify functionally meaningful co-primary measures in this area and will help to guide further evaluation of such measures.
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, UCLA, 300 Medical Plaza, Rm. 2263, Los Angeles, CA 90095-6968, USA. mgreen@ucla.edu
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.forename: Keith H
authors.initials: KH
authors.lastname: Nuechterlein
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kern
authors.forename: Lyle E
authors.initials: LE
authors.lastname: Baade
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Fenton
authors.forename: James M
authors.initials: JM
authors.lastname: Gold
authors.forename: Richard S E
authors.initials: RS
authors.lastname: Keefe
authors.forename: Raquelle
authors.initials: R
authors.lastname: Mesholam-Gately
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: Ellen
authors.initials: E
authors.lastname: Stover
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
mesh_terms: D026683:Advisory Committees; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000188:drug therapy; D032921:Consensus; D015195:Drug Design; D005069:Evaluation Studies as Topic; D005104:Expert Testimony; D006801:Humans; D009315:National Institute of Mental Health (U.S.); D009483:Neuropsychological Tests / Q000592:standards / Q000706:statistics & numerical data*; D011569:Psychiatric Status Rating Scales / Q000592:standards / Q000706:statistics & numerical data; D011594:Psychometrics; D011619:Psychotropic Drugs / Q000627:therapeutic use; D012016:Reference Values; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D011619:Psychotropic Drugs