0663 Content Validity and Meaningful Change on Patient-Reported Outcome Measures for Use in Obstructive Sleep Apnea

Abstract Introduction SynAIRgy (NCT05813275) was a randomized, double-blind, placebo-controlled, 26-week, parallel-arm Phase 3 trial of AD109 vs placebo in adults with mild-to-severe obstructive sleep apnea (OSA). Patient-reported outcomes (PROs) were among the assessed endpoints. This research sought to determine what participants perceive as meaningful change on the PROs and obtain evidence of their content validity. Methods Qualitative interviews via video conferencing were conducted with 32 participants within 3 days of completing SynAIRgy. PRO endpoints, including the PROMIS-Fatigue-8a (5 response categories), PROMIS-Sleep Impairment-8a (5 categories), Epworth Sleepiness Scale (ESS) (4 categories), Patient Global Impression of Severity (PGI-S) for Fatigue (5 categories), and Patient Global Impression of Change (PGI-C) for Fatigue (5 categories) were evaluated. During the concept elicitation (CE) portion of the interview, participants were asked questions exploring symptoms and disease impact. Number of categories of change deemed to be meaningful were also assessed. Concepts identified during the CE portion of the interview were mapped to each PRO to evaluate content validity. Analysis was conducted using qualitative software (MAXQDA). The study received IRB approval; participants provided informed consent. Results The majority of participants reported a one-point change on individual items from the PROMIS-Fatigue (61%-96%), PROMIS-Sleep Impairment (52%-96%), and ESS (62%-96%) as meaningful regardless of baseline response. 68%-100% stated a one-point change on the PGI-S would be meaningful; 83% found a change on the PGI-C of “a little better” to be meaningful. Mapping demonstrated that all PROs have strong concept coverage. Specifically, PROMIS-Fatigue, PGI-S, and PGI-C assess the concept of feeling fatigue/tired; all participants reported fatigue. PROMIS-Sleep Impairment assesses sleepiness, poor sleep, feeling alert upon waking, and feeling tired (88% had trouble sleeping/falling asleep/waking up, 66% reported daytime sleepiness, 50% reported not feeling rested upon awakening, and 100% reported feeling fatigue/tired). ESS assesses sleepiness in various situations; 66% reported daytime sleepiness. Conclusion This research confirmed robust concept coverage across all PROs for participants with OSA. Notably, a one-point change on the PROs represents a clinically meaningful improvement from the patient’s perspective. Establishing thresholds for meaningful change provides context for interpreting clinical significance for the PROs in OSA longitudinal studies. Support (if any) This research was supported by Apnimed, Inc.