Clinically Meaningful Score Difference and Meaningful Score Regions in Positive and Negative Syndrome Scale Total Score from Post Hoc Analyses of a Pivotal Phase III Clinical Trial
Background: HP-3070 (asenapine transdermal system) is indicated for adults with schizophrenia. The Food and Drug Administration recommends analyzing clinical outcome data to determine what score changes are clinically meaningful in patients (https://www.fda.gov/media/166830/download). The aim of this post hoc analysis was to determine the meaningful score difference (MSD) and meaningful score regions (MSR) in PANSS total score from the pivotal phase 3 study of HP-3070.
Methods: The MSD and MSR in PANSS score from baseline to endpoint (Week 6) were evaluated. Clinician-rated Clinical Global Impression-Severity (CGI-S =4,5,6, defined as “moderately ill”, “markedly ill”, or “severely ill”, respectively) and CGI-Improvement (CGI-I=1,2, defined as “very much improved” and “much improved”, respectively) scores were used as anchors.
The following were identified:
• MSD₁/MSD₂: change/% change in PANSS for ≥50% of responders (CGI-I=1,2)
• MSR: change/% change in PANSS by baseline CGI-S for [25%, 75%] of responders (CGI-I=1,2)
Results: In total, 616 patients were included. The mean (SD) baseline PANSS score was 96.6 (9.5). MSD₁ was -30, and MSD₂ was -32%. The MSR of change in PANSS by CGI-S=4,5,6 were [-36, -22.5]; [-37, -24]; and [-44, -27], respectively, and MSR of % change in PANSS were [-39%, -25%]; [-39%, -25%]; and [-41%, -25%], respectively.
Conclusion: A change of -32% was identified as the clinically MSD in change in PANSS score from baseline to Week 6. The MSD and MSR provide an estimate of expected treatment effect on schizophrenia patients in a population and can be a threshold to identify individual patients with clinically meaningful improvement.
