Site-independent confirmation of primary site-based PANSS ratings in a schizophrenia trial.

Abstract

Blinded, site-independent (remote) ratings from audio-digital recordings of site-based Positive and Negative Syndrome Scale (PANSS) interviews were obtained in a 5-week, randomized, double-blinded study assessing the safety, tolerability, and efficacy of KarXT (a fixed combination of xanomeline and trospium chloride) in hospitalized adults with schizophrenia experiencing an acute exacerbation of psychosis (EMERGENT-1; ClinicalTrials.gov identifier: NCT3697252). The blinded site-independent raters had no knowledge of site location, study visit, drug vs. placebo assignment, or any treatment emergent adverse events (TEAEs). Concordance analyses of 561 paired site-based and site-independent PANSS ratings across all visits revealed a high correlation (ICC = 0.775). Paired scoring differences were positively correlated with the PANSS total score (Spearman's rho = 0.37, p < 0.0001). Paired PANSS scores were available from 148 subjects at both the baseline and end of study visits (KarXT = 72, Placebo = 76). Site-based PANSS total scores (primary aim) revealed a significantly greater improvement from baseline in the KarXT group compared to the placebo group (p < 0.0001). The blinded site-independent PANSS total scores derived from listening to and scoring the recorded site-based PANSS interviews replicated this finding (p < 0.001) and yielded an overall predictive value of 85.1% for matching the site-based response/non-response outcomes. TEAE's have the potential to "unblind" site-based ratings. In this study, the site-independent raters were blinded to TEAEs, affirmed the site-based PANSS ratings, and mitigated concerns about possible functional unblinding of site-based raters. This method of blinded assessment via audio-digital recordings may have utility for other studies concerned with ratings precision and/or functional unblinding.

• Authors: Steven D Targum, Christopher Murphy, Alan Breier, Stephen K Brannan
• Journal: Journal of psychiatric research (J Psychiatr Res) Vol. 144 Pg. 241-246 (12 2021) ISSN: 1879-1379 [Electronic] England
• PMID: 34700212 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Antipsychotic Agents

Topics

• Adult
• Antipsychotic Agents (therapeutic use)
• Double-Blind Method
• Humans
• Psychotic Disorders (drug therapy)
• Schizophrenia (chemically induced, drug therapy)
• Treatment Outcome