title: Restrictive symptomatic inclusion criteria create barriers to clinical research in schizophrenia negative symptoms: an analysis of the CATIE dataset.
abstract: BACKGROUND
  Persistent negative symptoms are an important area of clinical research. However, there is limited consensus on how to define positive and negative symptom severity thresholds for inclusion in clinical trials. From the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset we evaluated the performance of varying baseline negative and positive symptom thresholds on baseline symptom severity, change from baseline, and negative symptom variance attributable to positive symptom change.
  
  
  METHODS
  In CATIE, we first identified the group of subjects lacking an exacerbation prior to study enrollment. Six subsets with varying baseline positive and negative symptom thresholds were then identified. Baseline characteristics were summarized; negative and positive symptom change from baseline through month 3 was calculated both as crude change and change adjusted for corresponding baseline scores. Sensitivity analyses and correlations were calculated to assess the extent to which negative symptom variance was attributable to positive symptom change.
  
  
  RESULTS
  More restrictive baseline symptom severity thresholds yielded a considerably smaller sample size and higher negative and lower positive symptoms at baseline. Unadjusted negative symptom change was greater with more restrictive criteria; when adjusted for baseline severity the magnitude of change was comparable across subsets. The amount of variance in negative symptom change attributed to positive symptom change was also comparable across subsets.
  
  
  CONCLUSIONS
  The use of restrictive positive and negative symptom thresholds yields a marked decrease in eligible sample size with no clear improvement in adjusted negative symptom change or amount of variance associated with positive symptom change.
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. Electronic address: edunayev@amgen.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Dunayevich
authors.affiliation: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
authors.forename: Chao-Yin
authors.initials: CY
authors.lastname: Chen
authors.affiliation: The Semel Institute for Neuroscience at University of California, Los Angeles, and the Desert Pacific Mental Illness Research, Education, and Clinical Center, PO Box 24DD5, Westwood Station, Los Angeles, CA 90024, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
authors.affiliation: Bar Ilan University, Ramat Gan, 22 Akiva Street, 43263 Raanana, Israel.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rabinowitz
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D035843:Biomedical Research / Q000379:methods*; D002986:Clinical Trials as Topic; D066264:Datasets as Topic; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012680:Sensitivity and Specificity
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotic effects; Clinical trial; Neurobehavioral signs and symptoms; Schizophrenia