Meaningful Within-Patient Change in Subjective Total Sleep Time in Patients with Insomnia Disorder: An Analysis of the Sleep Diary Questionnaire Using Data from Open-Label and Phase III Clinical Trials.

ABSTRACT

BACKGROUND: The Sleep Diary Questionnaire (SDQ), a modified version of the Consensus Sleep Diary, is a 17-item sleep diary for assessing subjective total sleep time (sTST total time spent asleep at night) and other sleep parameters in insomnia trials. sTST is a key parameter of efficacy in insomnia trials; however, the magnitude of improvement in this parameter that people with insomnia disorder consider clinically meaningful is unclear. OBJECTIVE: The aim of this study was to estimate meaningful within-patient change for sTST using clinical trial data. METHODS: Data were from an open-label trial of zolpidem and pooled data from a phase III placebo-controlled trial of daridorexant. In both trials, adults with moderate to severe insomnia completed the SDQ daily. Meaningful change in sTST was estimated in an anchor-based analysis using outcome measures that were correlated with change in weekly average sTST (Spearman correlation coefficient ≥ 0.30) the Insomnia Severity Index, patient global assessments and impressions of severity and change in daytime and night-time symptoms (PGA-S, PGI-S, PGI-C), and clinician global impressions of severity and change in patients' daytime symptoms (CGI-S, CGI-C). Meaningful within-patient change estimates were 'triangulated' to identify a value where they converged. RESULTS: In the open-label trial (N = 114), subjects with a 1-point or 1-step improvement on the anchors had mean increases in sTST of 60.1-83.2 min at day 8 and 55.5-68.2 min at day 15. For subjects with a 2-point or 2-step improvement on the anchors, mean increases in sTST were 79.6-81.4 min at day 8 and 80.1-93.5 min at day 15. In the phase III trial (N = 930), weekly average increases in sTST for subjects with a 1-point or 1-step improvement on the anchors were 39.3-46.7 min at month 1 and 47.3-58.3 min at month 3. For subjects with a 2-point or 2-step improvement on the anchors, mean increases in sTST were 60.7-76.2 min at month 1 and 70.1-87.7 min at month 3. Triangulation of these values supported a meaningful within-patient change threshold starting at 55 min. CONCLUSION: Increasing sTST is an important treatment outcome for people with insomnia. An increase in sleep time of approximately 55 min is meaningful to patients. CLINICAL TRIALS REGISTRATION NCT03056053 (17 February 2017) and NCT03545191 (4 June 2018).