Content validity and clinically meaningful change on patient-reported outcome measures for use in obstructive sleep...

AD109, an oral drug combination of aroxybutynin, an antimuscarinic, and atomoxetine, a norepinephrine reuptake inhibitor, has been tested in a Phase 3 randomized controlled trial for the treatment of obstructive sleep apnea (OSA) (SynAIRgy NCT05813275). This study aimed to evaluate the content validity of the patient-reported outcome measures (PROMs) administered during the study and to determine what participants perceive as clinically meaningful change on the PROMs.

Qualitative exit interviews were conducted with 32 participants within 10 days of completing the trial. PROMs included 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). Participants were asked questions about symptoms and disease impact and then concepts identified were mapped to each PROM to evaluate content validity. Participants were also asked about the amount of change they considered to be clinically meaningful on each PROM.

Mapping demonstrated all PROMs have strong concept coverage. Most participants reported a one-point change on response options for individual items from the PROMIS-Fatigue (61%-96%), PROMIS-Sleep Impairment (52%-96%), and ESS (62-96%) was clinically meaningful, regardless of baseline response. Sixty-eight percent to 100% viewed a one-point PGI-S change to be clinically meaningful; 83% indicated a PGI-C rating of "a little better" was clinically meaningful.

These results confirm the content validity of all the PROMs in individuals with OSA. A one-point change on PROMs represents a clinically meaningful improvement from the patient's perspective.