Assessment of Negative Symptoms in Clinical Trials of Acute Schizophrenia: Test of a Novel Enrichment Strategy

Abstract Drug trials for negative symptoms in schizophrenia select patients based on the severity and stability of symptoms, using criteria that are not suitable acute exacerbation schizophrenia. Here we present a method to prognostically enrich subjects having predefined factor structure PANSS apply it measurement specifically A vector 1335 elements between- within-item variances, covariances, differences items was created calculate an index heterogeneity predetermined symptom construct PANSS. Using prerandomization scores across N = 4876 13 schizophrenia, demonstrate ability subpopulation greatest amount variance explained 7-items Marder (MPNS) construct. Network analyses enriched MPNS confirm were most influential overall psychopathology, distinct from without As expected D2 antagonists, drug-placebo with lurasidone specific In contrast, novel TAAR1 agonist ulotaront demonstrated improvements which subpopulation. These results utility prognostic enrichment strategy can address clinical trials, where be selected basis greater likelihood measured (negative symptoms) related disorder (schizophrenia). ClinicalTrials.gov Identifiers: NCT0296938, NCT00088634, NCT00549718, NCT00615433, NCT00790192