GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS^©): psychometric properties and clinically meaningful thresholds as assessed in the Phase 3 DeFi randomized controlled clinical trial

Purpose: The GODDESS^© tool was developed to assess Desmoid Tumor/Aggressive Fibromatosis (DT/AF) symptom severity and impact on patients' lives. This study evaluated GODDESS^©'s cross-sectional and longitudinal measurement properties.

Methods: The Phase 3, randomized placebo-controlled, DeFi study (NCT03785964) of nirogacestat in DT/AF was used to assess GODDESS^©'s reliability, construct validity, responsiveness, and estimate of meaningful change thresholds (MCTs). Other patient-reported outcome (PRO) measures included Patient Global Impression of Severity (PGIS) in DT/AF symptoms, EORTC QLQ-C30, Brief Pain Inventory Short Form, and PROMIS Physical Function short-form 10a v2.0 plus 3 items.

Results: DeFi participants (N = 142) had a median age of 34 years (range: 18-76) and were mostly female (64.8%), with extra-abdominal (76.8%) or intra-abdominal tumors (23.2%). The GODDESS^© symptom/impact scales showed internal consistency at baseline, cycles 4 and 7 (Cronbach's α > 0.70) and test-retest reliability (intra-class correlation coefficient > 0.85). GODDESS^© scales correlated moderately to highly with PRO measures capturing similar content and differentiated among PGIS and Eastern Cooperative Oncology Group groups. GODDESS^© scales detected improvement over time. For the total symptom score, a 1.30-point decrease was estimated as the within-person MCT and a 1.00-point decrease as the between-group MCT. For the physical functioning impact score, estimated within- and between-group MCTs were 0.60-point and 0.50-point decreases, respectively. Few participants exhibited symptom worsening.

Conclusion: GODDESS^© was found to be reliable, valid, responsive, and interpretable as a clinical trial endpoint in the pooled sample of DT/AF patients. Estimated MCTs can be used to define responders and assess group-level differences in future, unblinded, efficacy analyses.

Trial registration number and registration date: NCT03785964; December 24, 2018.