Relationship Between Efficacy Endpoints and Measures of Functional Status and Health-Related Quality of Life (HRQoL) in Obstructive Sleep Apnea patients Treated for Excessive Sleepiness
Mathias SD, Crosby RD, Drake C, Bron M, Bujanover S, Menno D, and Villa KF. Relationship between efficacy endpoints and measures of functional status and health-related quality of life (HRQoL) in obstructive sleep apnea patients treated for excessive sleepiness. J Sleep Res 2018; 27:300-301.
J Sleep Res
Objectives/Introduction: A 12-week, double-blind, randomized, placebo-controlled Phase 3 trial in patients with obstructive sleep apnea associated with excessive sleepiness showed that solriamfetol doses 37.5, 75, 150 and 300 mg resulted in statistically significant, clinically meaningful improvements on the Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT), and Patient Global Impression of Change (PGI-C) (except 37.5 mg PGI-C). In addition, significant improvements in functional status and health-related quality of life (HRQoL) were observed with the 150 and 300 mg doses. Given that significant improvements in efficacy endpoints do not always translate into improvements in functional/HRQoL outcomes, the relationship between efficacy and functional/HRQoL outcomes was examined. Methods: In all participants, the ESS, MWT, Functional Outcomes of Sleep Questionnaire-short version (FOSQ-10), Work Productivity and Activity Impairment Questionnaire (WPAI), EuroQoL 5-Dimension (EQ-5D 5L), Short-Form (SF)-36v2 (SF36-v2) and PGI-C were administered at baseline (except PGI-C), Weeks 4, 8 and 12. Pearson correlation coefficients were calculated, pooling across all treatment groups, to assess the relationship between changes in efficacy and functional/HRQoL outcomes between baseline and Week 12 (change scores). Correlations were reported for those functional/HRQoL outcomes with significant (nominal) improvements at Week 12. Values of 0.10 to0.50 reflect low, moderate, and high correlations, respectively. Results: Data from the modified intent to treat (mITT) population were analyzed (n = 459). Correlations (rho) for change scores were high between ESS and FOSQ-10 (-0.541), and moderate between ESS and SF-36v2 Vitality (-0.489), activity impairment (AI) measured by WPAI (0.441), work productivity loss (WPL) measured by WPAI (0.334) and SF-36v2 Role-Physical (-0.332). Correlations were low between MWT and SF-36v2 Vitality (0.273), SF-36v2 Role-Physical (0.184), FOSQ-10 (0.163), AI (-0.136) and WPL (-0.091). PGI-C correlations were high with SF-36v2-Vitality (-0.581) and FOSQ-10 (-0.529), and moderate between PGI-C and AI (0.476) and WPL (0.398) and SF-36v2 Role-Physical (-0.371). Conclusions: Changes in the efficacy endpoints for ESS, MWT and PGI-C from baseline to Week 12 were associated with changes in several functional and HRQoL outcomes for solriamfetol-treated OSA patients. Associations between self-reported efficacy endpoints (ESS and PGI-C) and measures of functional/HRQoL status were stronger than associations with the objective efficacy endpoint (MWT).