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

Abstract

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.

Capturing Patient Voice to Improve Outcomes That Matter to Patients with Desmoid Tumor

“…Validity and reliability analyses for DTSS and DTIS scales using data from DeFi indicated that all scores were valid and reliable measures of DT symptomology and impact, and the recommended reliability thresholds for construct validity were met. 48 Further, GODDESS proved sufficiently responsive regardless of low patient symptomology at baseline. Based on these findings, GODDESS became the first validated DT-specific PRO measure designed to meet FDA regulatory requirements.…”

“…In order to better capture the patient experience and treatment effects in DT, the GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS © ) was developed through a collaboration of the Desmoid Tumor Research Foundation and Memorial Sloan Kettering Cancer Center. 48 The goal was to construct a novel regulatory and clinical trial endpoint uniquely developed for patients with DT to complement existing general PRO measurements, such as the EORTC QLQ-C30. 14 The process began with concept elicitation interviews of patients who were asked to spontaneously identify symptoms and/or impacts that they attributed to DT.…”

“…In addition, meaningful change thresholds (MCTs) for improvement of symptom and impact domain scales were estimated, which potentially may be of use in identifying responders and non-responders in clinical trials. 48

Figure 2 GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS © ) PRO Measure. 48 aAdministered only to those reporting intra-abdominal tumor location in item 8. b 11-point scale where 0 indicates “none” and 10 indicates “as bad as you can imagine”, with a 24-hour recall period.

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“… 48

Figure 2 GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS © ) PRO Measure. 48 aAdministered only to those reporting intra-abdominal tumor location in item 8. b 11-point scale where 0 indicates “none” and 10 indicates “as bad as you can imagine”, with a 24-hour recall period. c 5-point Likert scale ranging from “none of the time” to “all of the time”.

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Desmoid Tumors: Current Perspective and Treatment

“…Significantly better scores were recorded in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 physical and role functioning scores, as well as quality of life scores. The GODDESS score (GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale) is an innovative tool for the assessment of patient-reported signs and symptoms that was used in the DeFi trial [ 39 ]. The BPI-SF (Brief Pain Inventory-Short Form) pain intensity score recorded a significantly better improvement in the average worst pain intensity with nirogacestat, indicating better patient outcomes with the GSI than with placebo.…”