A minimal clinically important difference for the sleep inertia visual analog scale in idiopathic hypersomnia

Measurement tools for sleep inertia, a common and important idiopathic hypersomnia symptom, are limited. For individuals with idiopathic hypersomnia, this post hoc analysis proposes a minimal clinically important difference (MCID) for the Sleep Inertia Visual Analog Scale (SI-VAS), which assesses difficulty waking up. Data from the pivotal phase 3, double-blind, placebo-controlled, randomized withdrawal study (NCT03533114) of low-sodium oxybate in adults with idiopathic hypersomnia were used to estimate an SI-VAS MCID anchored to the Patient Global Impression of Change (PGIc), Idiopathic Hypersomnia Severity Scale (IHSS), and Functional Outcomes of Sleep Questionnaire (FOSQ-10). Of 109 participants included, majority female (69.7%) and White (81.7%), most were at least moderately ill (95%) per baseline Clinical Global Impression of Severity. SI-VAS score changes were strongly associated with PGIc levels (Kruskal-Wallis test statistic, 110.2; P<0.0001). Estimated mean (SE) difference in SI-VAS scores between consecutive PGIc levels was 10.9 (0.8) mm, suggesting an MCID estimate of 10-12 mm. SI-VAS was also highly correlated with IHSS (Pearson r, 0.79; P<0.0001) and FOSQ-10 (Pearson r, -0.74; P<0.0001). Mean (SE) SI-VAS change per 4-unit IHSS change (MCID) was 6.0 (0.3) mm and per 2-unit FOSQ-10 change (cutpoint) was 8.5 (0.5) mm. Establishing an MCID strengthens the SI-VAS value, adds context for findings related to sleep inertia in individuals with idiopathic hypersomnia from the phase 3 study, and aids clinicians in identifying clinically meaningful changes in sleep inertia to improve patient outcomes. Registry: ClinicalTrials.gov; Identifier: NCT03533114; Name: A Multicenter Study of the Efficacy and Safety of JZP-258 in the Treatment of Idiopathic Hypersomnia (IH) With an Open-label Safety Extension; URL: https://www.clinicaltrials.gov/study/NCT03533114.