Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Daridorexant shows moderate benefit over placebo in improving insomnia symptoms, with statistically significant reductions in wake after sleep onset (WASO) and latency to persistent sleep (LPS) at 1 and 3 months. However, the long-term effects beyond 12 months remain uncertain, limiting the rating to A.
Cost effectiveness
The cost-effectiveness estimates for daridorexant fall within NICE’s acceptable range, with an ICER of £25,383 per QALY gained. This suggests a clear economic value under common thresholds, despite some uncertainties in the model.
Quality of life
The evidence indicates moderate improvements in HRQoL, as measured by the Insomnia Severity Index (ISI) and other subjective assessments. However, the clinical significance of these improvements is debated, particularly regarding the placebo effect.
Supporting Domains
Safety and Adverse Effects
Daridorexant has a favorable safety profile, with treatment-emergent adverse events reported at rates comparable to placebo. Serious adverse events were rare, indicating good tolerability.
Comparator Selection
The primary comparator was placebo, which is appropriate given the positioning of daridorexant as a second-line treatment after CBTi. However, the absence of direct comparisons with other active treatments limits the robustness of the evidence.
Patient Population and Subgroups
The trial population was somewhat narrow, primarily consisting of individuals meeting specific DSM-5 criteria for insomnia. This raises concerns about generalizability to the broader Healthcare population, particularly regarding those with comorbid conditions.
Care Pathway Integration
Daridorexant can be integrated into existing care pathways with minor adjustments, as it is positioned as a second-line treatment when CBTi is unavailable or ineffective. The committee noted the importance of GP training for effective implementation.
Resource Use and Cost Implications
The economic model indicates that daridorexant is likely to be resource-efficient, with manageable budget impacts aligned with Healthcare planning. However, uncertainties regarding long-term costs remain.
Evidence Quality and Robustness
The evidence base includes Phase 3 RCTs with a substantial sample size, although there are some methodological concerns and gaps in long-term data. Overall, the evidence is credible but not without limitations.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effectiveness of daridorexant and its applicability to the broader population, particularly concerning those with mental health conditions. This uncertainty affects the overall assessment.
