Estimating Meaningful Change Thresholds (MCTs) for EORTC Scales in a Phase 3 Trial in Participants With Inoperable or Metastatic Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer
Author(s)
Zhu Y1, Bell J2, Daskalopoulou C3, Ivanescu C4, Lai R2, Arizmendi C5, Mapiye D6, Shi L7, Munegowda MA8, Verma D6, Khan S2
1AstraZeneca, Waltham, MA, USA, 2AstraZeneca, Gaithersburg, MD, USA, 3IQVIA, Athens, Greece, 4IQVIA, Amsterdam, NH, Netherlands, 5AstraZeneca, Durham, NC, USA, 6AstraZeneca, Central Cambridge, UK, 7AstraZeneca, Memphis, TN, USA, 8AstraZeneca, Mississauga, ON, Canada
Presentation Documents
OBJECTIVES: Interpretation of clinical trial data is limited without defined MCTs for within-participant change and between-group difference of study endpoints. This study aimed to estimate MCTs for selected European Organisation for Research and Treatment of Cancer (EORTC) scales from the TROPION-Breast01 trial of advanced breast cancer (NCT05104866).
METHODS: Pre-specified analyses were performed to define MCTs for selected EORTC scales, including Global Health Status/Quality of Life (GHS/QoL), functioning (physical, role, emotional, cognitive, social), pain, fatigue, arm, and breast symptoms using pooled blinded data from baseline, weeks 6 and 12. Patient Global Impression of Severity and Patient Global Impression of Change were used as anchors. Anchor appropriateness was assessed via Spearman correlations, with values ≥0.371 considered adequate. Distribution and anchor-based methods were investigated. Test-retest and internal consistency reliability coefficients, required as input for the distribution-based methods, were examined. The within-participant MCT estimates were additionally evaluated against the possible amount of change observable on each scale.
RESULTS: In total, 513 and 384 participants provided evaluable scores at baseline and across all timepoints, respectively. Anchor correlations were low (<0.371) for majority of scales, thus anchor-based estimates were given limited consideration. Thresholds were estimated via distribution-based approaches, supported by adequate reliability for most scales. Within-participant threshold for deterioration was 11.1 for fatigue and arm symptoms, 13.3 for physical functioning, and 16.6 for GHS/QoL, functioning (role, emotional, cognitive, social), pain, and breast symptoms. GHS/QoL, physical functioning, and pain were employed as trial secondary endpoints via time to deterioration analyses. The between-group difference MCT range was 6.6–15.6.
CONCLUSIONS: MCTs were derived for the selected EORTC scales and helped Patient-Reported Outcome (PRO) endpoint interpretation in this trial. MCTs may also be used in routine care to better understand the significance of longitudinal change in patient outcomes.
Conference/Value in Health Info
Value in Health, Volume 27, Issue 6, S1 (June 2024)
Code
PCR50
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas