A patient-centric benefit-risk assessment of daridorexant for the treatment of insomnia disorder using patient preference data collected in two phase 3 clinical trials

• Patient preference information can facilitate the interpretation of clinical data. • We conducted a patient-centric benefit-risk assessment of an insomnia treatment. • Outcomes and preference data from two phase 3 trials were jointly analyzed. • Daridorexant’s benefits likely outweigh its risks from the patient perspective. • With its novel approach, this study serves as an example for future studies. To conduct a patient-centric benefit-risk assessment of daridorexant vs. placebo for insomnia disorder treatment. A quantitative benefit-risk assessment (qBRA) combined patient preference information and clinical data collected in two multicenter placebo-controlled phase 3 trials. The qBRA weighted efficacy and adverse event data collected in the daridorexant and placebo trial arms based on the acceptable benefit-risk trade-offs patients would be willing to make in a discrete choice experiment. The preference-weighted trial arms were used to test the total net benefits of daridorexant 50 mg and daridorexant 25 mg vs. placebo. Sensitivity analyses accounted for uncertainty in both clinical trial and patient preference data. Preferences of 602 trial participants (68.1 % female, mean age 58.6 years) were used in the qBRA analysis. Both daridorexant 25 mg (net benefit [standard error {SE}] = 0.097 [0.022]) and daridorexant 50 mg (net benefit [SE] = 0.197 [0.025]) had a significantly higher net benefit than placebo (both p < 0.001). Time to fall asleep, daytime functioning, and total time asleep provided added value for daridorexant over placebo and outweighed potential side effects. The sensitivity analyses accounting for differences in both clinical trial and patient preference data indicated that both doses of daridorexant would still be preferred over placebo. Even when accounting for uncertainty in clinical data and patients’ preferences, both daridorexant 25 mg and 50 mg were likely to have a positive benefit-risk balance from the patient’s perspective.