The Clinically Meaningful Score Difference and Meaningful Score Regions in Positive and Negative Syndrome Scale Total Score from Post Hoc Analyses of a Phase 3 Pivotal Clinical Trial of Transdermal Asenapine in Patients with Schizophrenia.

内容摘要

HP-3070, the first asenapine transdermal system (patch), is indicated for adults with schizophrenia. The US Food and Drug Administration recommends analyzing clinical outcome data by using meaningful score difference (MSD) and meaningful score regions (MSRs) to determine what score changes are clinically meaningful to patients. This post hoc analysis aimed to determine the MSD and MSRs in Positive and Negative Syndrome Scale (PANSS) total score from the pivotal phase 3 study of HP-3070. Clinician-Rated Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I) scores were used as anchors to quantify improvement from baseline to Week 6 in PANSS total score. The following were identified: MSD-change and percentage change in PANSS for ≥50% of responders (CGI-I=1,2) and MSRs-change and percentage change in PANSS by baseline CGI-S for 25th and 75th percentiles of responders. In total, 616 patients were evaluated. The mean (SD) baseline PANSS total score was 96.6 (9.5). MSD of change in PANSS score was -30 points. MSDs of percentage change in PANSS scores were -32% and -46% based on calculations without and with adjustment for the scale's minimum score, respectively. For all responders defined as CGI-I=1 or 2, MSRs of change in PANSS score ranged from -37 to -24. MSRs of percentage change in PANSS score ranged from -39% to -25% without adjustment and -57% to -37% with adjustment. The MSD and MSRs provide an estimate of expected treatment effect on schizophrenia patients in a population and serve as a threshold to identify individual patients with clinically meaningful improvement. These results contribute to the ongoing discussion of what constitutes a clinically meaningful response in patients with an acute episode of schizophrenia and provide an estimate of the expected treatment effect of HP-3070.