Assessing the meaningful change threshold of Quality of Life in Depression Scale using data from two phase 3 studies of esketamine nasal spray

Abstract

Background: Major depressive disorder (MDD) directly impacts patients' lives including symptoms, functioning and health-related quality-of-life (HRQoL). Patient-reported outcomes can capture these impacts, however interpretation of clinical meaningfulness of these measurements are often not readily available. Meaningful change thresholds (MCTs) can be derived for clinical outcome assessments to quantify the change in symptoms that is meaningful to the patient following pharmacologic treatment or other interventions. The objective of this analysis was to determine the within-patient MCT of the self-reported Quality-of-Life in Depression Scale (QLDS) among patients with MDD and active suicidal ideation with intent (MDSI) using an anchor-based approach.

Methods: Data from 2 randomized phase-3 trials of esketamine nasal spray (ASPIRE I and ASPIRE II) were analyzed. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary anchor with three different severity criteria. Other anchor variables utilized were Clinical Global Impression of Severity of Suicidality-revised version, Clinical Global Impression of Imminent Suicide Risk, and EuroQol Visual Analog Scale [EQ-VAS]. Spearman correlation coefficients between the change in QLDS and anchor variables were calculated. The mean change in QLDS score at Day 25 from baseline was calculated based on the categorical change in the anchor. Coefficient yield from linear regression of the mean changes in EQ-VAS and QLDS, and distribution-based approach with ½ SD of change in QLDS were considered.

Results: In ASPIRE I, mean (SD) improvement in QLDS score among patients with one category improvement in MADRS from baseline to Day 25 was - 8.22 (8.87), - 8.30 (9.01), and - 8.20 (8.92) using severity criteria #1, #2, and #3, respectively. Patients who achieved a 7-point improvement (MCT) in EQ-VAS yielded a mean - 9.69-point improvement in QLDS at Day 25. The ½ SD of change in QLDS was 5.63. Similar results were obtained for ASPIRE II. The MCTs identified using multiple anchors across both trials ranged from - 11.4 to - 6.7 and had an overall mean of - 7.90 (ASPIRE I) and - 7.92 (ASPIRE II). Thus, an 8-point change was recommended as the MCT for QLDS.

Conclusion: The recommended MCT will help quantify within-person changes in HRQoL using patient-reported QLDS and determine meaningful treatment benefit in an MDD patient population with acute suicidal ideation or behavior.

Trial registration: Name of the registry: ClinicalTrials.gov.

Trial registration number: ASPIRE I (NCT03039192), ASPIRE II (NCT03097133). Date of registration: February 01, 2017; March 31, 2017. URL of trial registry record: https://ichgcp.net/clinical-trials-registry/NCT03039192 ; https://ichgcp.net/clinical-trials-registry/NCT03097133 .

Keywords: Anchor-based approach; Major depressive disorder; Meaningful change threshold; Quality of Life in Depression.

Conflict of interest statement

All authors are employees of Janssen and may own stock or stock options.

© 2022. The Author(s).

Figures

Fig. 1

ASPIRE I–mean change in QLDS score from baseline to Day 25 using MADRS as an anchor. Values are represented as mean ± 95% CI. MADRS was categorized as: severity criteria #1—no depression (score 0–12), slight depression (score 13–21), moderate depression (score 22–28), and severe depression (score > 28–60); severity criteria #2—no depression (score 0–6), mild depression (score 7–19), moderate depression (score 20–34), and severe depression (score > 34–60); and severity criteria #3—no depression (score 0–12), mild depression (score 13–17), moderate depression (score 18–34), and severe depression (score > 34–60). CAT Category, CI Confidence Interval, IMP Improvement, MADRS Montgomery–Åsberg Depression Rating Scale, QLDS Quality of Life in Depression Scale

Fig. 2

ASPIRE II–mean change in QLDS score from baseline to Day 25 using MADRS as an anchor. Values are represented as mean ± 95% CI. MADRS was categorized as: severity criteria #1—no depression (score 0–12), slight depression (score 13–21), moderate depression (score 22–28), and severe depression (score > 28–60); severity criteria #2—no depression (score 0–6), mild depression (score 7–19), moderate depression (score 20–34), and severe depression (score > 34–60); and severity criteria #3—no depression (score 0–12), mild depression (score 13–17), moderate depression (score 18–34), and severe depression (score > 34–60). CAT Category, CI Confidence Interval, IMP Improvement, MADRS Montgomery–Åsberg Depression Rating Scale, QLDS Quality of Life in Depression Scale

Fig. 3

Meaningful change thresholds of QLDS using anchor- and distribution-based approach. Values represent MCT for various categories or points of improvement in QLDS score from Baseline to Day 25. For all MADRS severity criteria—one-category improvement and for EQ-VAS—7-point improvement. EQ-VAS EuroQol Visual Analog Scale, MADRS Montgomery–Åsberg Depression Rating Scale, MCT meaningful change threshold; QLDS Quality of Life in Depression Scale, SD Standard Deviation

Fig. 4

Cumulative distribution function of change from baseline to Day 25 in QLDS score stratified by MADRS change category at Day 25. A, B: Severity Criteria #1; C, D: Severity criteria #2; E, F: Severity Criteria #3 (see Table 1 for details). BL Baseline, IMP Improvement, MADRS Montgomery–Åsberg Depression Rating Scale, QLDS Quality of Life in Depression Scale