title: Noninferiority of perphenazine vs. three second-generation antipsychotics in chronic schizophrenia.
abstract: Noninferiority analysis is a statistical method of growing importance in comparative effectiveness research that has rarely been used in psychopharmacology. This method is used here to evaluate whether first-generation antipsychotics are clinically not inferior to second-generation antipsychotics (SGAs) using data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). A conservative noninferiority margin (NIM) on the Positive and Negative Syndrome Scale (PANSS) was derived from the smallest published value for the minimal clinically important difference, further reduced by 25%. This NIM was used to assess whether perphenazine is noninferior to olanzapine, risperidone, and quetiapine on the basis of the 95% confidence intervals of differences in mean PANSS outcomes (N = 1049). Perphenazine was noninferior to all three SGAs during 18 months of intention-to-treat analysis and in several subanalyses. Noninferiority can be evaluated from studies designed as superiority trials. Power was available in the CATIE to conduct noninferiority analysis.
authors.affiliation: *VA New England Mental Illness Research and Education Center, West Haven, CT; and †Department of Psychiatry, and ‡Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT.
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenheck
authors.forename: Haiqun
authors.initials: H
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D002908:Chronic Disease; D003987:Dibenzothiazepines / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010546:Perphenazine / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000627:therapeutic use; D018401:Sample Size; D012559:Schizophrenia / Q000188:drug therapy*; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D010546:Perphenazine; D018967:Risperidone; D000077152:Olanzapine