Background and Objective Chronic insomnia has major consequences for daytime functioning, yet no fully validated patient-reported outcome instrument for once-daily assessments is available to measure these consequences. This study describes the development and psychometric evaluation of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Methods The Daytime Insomnia Symptom Scale (DISS), an existing 20-item instrument for assessing daytime functioning, was modified to give an 18-item version of the IDSIQ (IDSIQ-18) based on iterative qualitative interviews with 54 subjects with insomnia and expert input. The construct validity and other psychometric properties of the IDSIQ-18 were analyzed based on an interventional study (NCT03056053) in which subjects with insomnia received zolpidem (5 or 10 mg) daily for 2 weeks and an observational study among subjects with no diagnosis of insomnia (good sleepers). Participants in both studies completed the IDSIQ-18 daily for 2 weeks. Exit interviews were conducted with a sample of subjects who completed the interventional study to elicit concepts defining the experience of insomnia, to assess understanding of the response scales, and to determine meaningful change thresholds. Exploratory factor analysis and Rasch analysis were conducted to further assess the structure and latent model for the scoring of the final IDSIQ instrument. Further psychometric evaluation of the final IDSIQ was then conducted. Results Subjects in both the interventional study ( N = 114) and observational study ( N = 103) were predominantly female (65% for subjects with insomnia and 60% for good sleepers). Mean age was 51 years for subjects with insomnia and 45 years for good sleepers. Subjects in the exit interviews ( N = 41) demonstrated a good understanding of the IDSIQ-18 response scales. Day 1 mean scores were higher (worse) in subjects with insomnia compared with good sleepers. Based on inter-item correlation, exploratory factor, and Rasch analyses and review of the qualitative data, four items were removed. This yielded the final IDSIQ, with 14 items comprising three domains: Alert/Cognition, Mood, and Sleepiness. The domain structure was determined in a confirmatory factor analysis. Evidence of internal consistency reliability was strong: day 1 Cronbach’s alpha was 0.917 for IDSIQ total score and 0.806–0.918 for the domains. Test-retest reliability, assessed for subjects with insomnia with no change on the Patient Global Assessment of Disease Severity scale between day 1 and day 8, was also good (intra-class correlation coefficient 0.856–0.911). Meaningful change thresholds derived for this sample using anchor-based approaches were 20 for IDSIQ total score, 9 for the Alert/Cognition domain, 4 for the Mood domain, and 4 for the Sleepiness domain. Conclusions These studies, which closely followed Food...

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Background Treatment decisions for multiple sclerosis (MS) are influenced by many factors such as disease symptoms, comorbidities, and tolerability. Objective To determine how much relapsing MS patients were willing to accept the worsening of certain aspects of their MS in return for improvements in symptoms or treatment convenience. Methods A web-based discrete choice experiment (DCE) was conducted in patients with relapsing MS. Multinomial logit models were used to estimate relative attribute importance (RAI) and to quantify attribute trade-offs. Results The DCE was completed by 817 participants from the US, the UK, Poland, and Russia. The most valued attributes of MS therapy to participants were effects on physical fatigue (RAI = 22.3%), cognitive fatigue (RAI = 22.0%), relapses over 2 years (RAI = 20.7%), and MS progression (RAI = 18.4%). Participants would accept six additional relapses in 2 years and a decrease of 7 years in time to disease progression to improve either cognitive or physical fatigue from “quite a bit of difficulty” to “no difficulty.” Conclusion Patients strongly valued improving cognitive and physical fatigue and were willing to accept additional relapses or a shorter time to disease progression to have less fatigue. The impact of fatigue on MS patients’ quality of life should be considered in treatment decisions.

Background: In the OPTIMUM trial in patients with relapsing MS, treatment differences in annualized relapse rate (ARR, 0.088) and change in fatigue at week 108 (3.57 points, measured using the Fatigue Symptoms and Impacts Questionnaire–Relapsing Multiple Sclerosis, symptom domain (FSIQ-RMS-S)) favored ponesimod over teriflunomide. However, the importance of the fatigue outcome to patients was unclear. Objective: To assess the importance of the OPTIMUM FSIQ-RMS-S results using data from an MS discrete choice experiment (DCE). Methods: The DCE included components to correlate levels of physical and cognitive fatigue with FSIQ-RMS-S scores. Changes in relapses/year and time to MS progression equivalent to the treatment difference in fatigue in OPTIMUM were determined for similar fatigue levels as mean baseline fatigue in OPTIMUM. Results: DCE participants would accept 0.06 more relapses/year or a 0.15–0.17 year decrease in time to MS progression for a 3.57-point difference in physical fatigue on the FSIQ-RMS-S. To improve cognitive fatigue by 3.57-points on the FSIQ-RMS-S, DCE participants would accept 0.09–0.10 more relapses/year or a 0.24–0.28 year decrease in time to MS progression. Conclusion: MS patients would accept 0.06 more relapses/year to change their fatigue by a similar magnitude as the between-treatment difference observed in the OPTIMUM trial.

Study Objectives To elicit the trade-offs patients are willing to make between benefits and risks of medications for chronic insomnia, with the purpose of allowing a patient-centric interpretation of clinical trial data. Methods A discrete choice experiment (DCE) was included in the two placebo-controlled phase III trials that evaluated the efficacy and safety of daridorexant. The DCE design was informed by a two-phase qualitative study, followed by qualitative and quantitative pilot testing before fielding. Relative attribute importance (RAI) and acceptable trade-offs between benefits and risks were obtained using a mixed logit model. Results Preferences were elicited from 602 trial participants (68.1% female, aged 58.6±14.5 years). Preferences were most affected by daytime functioning (RAI=33.7%) as a treatment benefit and withdrawal symptoms (RAI=27.5%) as a risk. Patients also valued shorter sleep onset (RAI=6.4%), longer sleep maintenance (RAI=5.4%), reduced likelihood of abnormal thoughts and behavioral changes (RAI=11.3%), reduced likelihood of dizziness/grogginess (RAI=9.2%), and reduced likelihood of falls at night (RAI=6.5%). Patients were willing to make trade-offs between these attributes. For example, they would accept an additional 18.8% risk of abnormal thoughts and behavioral changes to improve their daytime functioning from difficult to restricted and an additional 8.1% risk of abnormal thoughts and behavioral changes to avoid moderate withdrawal effects. Conclusions Patients with insomnia were willing to make trade-offs between multiple benefits and risks of pharmacological treatments. Because patients valued daytime functioning more than sleep latency and duration, we recommend that functional outcomes and sleep quality be considered in treatment development and evaluation.