Determining Meaningful Change in Depression Symptoms Assessed With the Patient Health Questionnaire (PHQ-9) and Sheehan Disability Scale (SDS) Among Patients With Treatment Resistant Depression in Trials of Esketamine Nasal Spray

Introduction: Meaningful change thresholds (MCT) derived from clinical outcome assessments quantify the change amount during pharmacologic treatment that is meaningful to the patient. We assessed PHQ-9 and SDS meaningful change to determine MCT using anchor-based methods and compared meaningful differences in patients within different treatment arms.

Methods: TRANSFORM 1 (NCT02417064) and -2 (NCT0241858) were Phase 3 trials that evaluated the efficacy and safety of fixed and flexible doses of esketamine nasal spray (56 mg or 84 mg) in combination with a newly-initiated oral antidepressant in treatment resistant depression (TRD) patients. Patient-reported outcome instruments were the PHQ-9 and SDS. Clinical Global Impression-Severity (CGI-S) was the analysis anchor which used blinded data from TRANSFORM-1. Patients were classified into change categories (15 levels, from -7 to 7 where negative change scores indicate improvement). Cumulative Distribution Function (CDF) curves were generated using unblinded TRANSFORM-2 data.

Results: TRANSFORM-1: the correlation between change on the CGI-S and change on the PHQ-9 at Day 28 was high (> 0.60) with anchor-based MCTs ranging from 5 to 8 points. The magnitude of change (standardized effect size estimate within-subject change) for patients improving was high (> 0.80). Similar results were observed on the SDS, suggesting an MCT ranging from 3 to 7 with an MCT value of 5 points. CDF curves from TRANSFORM-2 showed separation between treatments.

Conclusions: This study is the first to derive a MCT on the PHQ-9 and SDS in TRD to measure meaningful change from the patient perspective using regulatory-preferred psychometric anchor-based methodology.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.