Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence shows that solriamfetol reduces excessive daytime sleepiness compared with placebo, but there is no direct comparison with standard treatments like dexamfetamine or methylphenidate. The indirect comparisons with pitolisant and sodium oxybate are limited and add uncertainty to its clinical effectiveness.
Cost effectiveness
The cost-effectiveness estimates for solriamfetol compared with dexamfetamine or methylphenidate are highly uncertain and likely exceed NICE’s acceptable thresholds. However, it is considered cost-effective compared to pitolisant and sodium oxybate.
Quality of life
There was no significant change in quality of life measures (EQ-5D, FOSQ-10, SF-36) between solriamfetol and placebo. The assessment of quality of life was deemed uncertain due to the methodology used, which may not adequately capture the impact of treatment.
Supporting Domains
Safety and Adverse Effects
The incidence of adverse events leading to treatment discontinuation was low in the trials, and the safety profile of solriamfetol appears favorable compared to other treatments. However, the lack of data for dexamfetamine and methylphenidate introduces some uncertainty.
Comparator Selection
The comparators used in the analysis were appropriate, but the lack of direct clinical trial data for dexamfetamine and methylphenidate limits the robustness of the comparisons. The committee acknowledged that the relevant comparators depend on their position in the treatment pathway.
Patient Population and Subgroups
The trial population was generally representative of the narcolepsy population seen in Healthcare practice, although there were some limitations in subgroup analyses due to small sample sizes. The results are considered generalizable.
Care Pathway Integration
Solriamfetol can be integrated into existing treatment pathways with minor adjustments, as it is positioned as a second-line treatment after modafinil. The committee noted that it fits well within the current clinical practice.
Resource Use and Cost Implications
The economic model did not fully account for the likely increased healthcare resource use from adverse events associated with dexamfetamine and methylphenidate, leading to concerns about the overall resource burden.
Evidence Quality and Robustness
The evidence base is limited by the reliance on a single trial (TONES 2) and indirect comparisons, which introduces uncertainty. The trial design and data completeness raise some methodological concerns.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the cost-effectiveness estimates and the treatment pathway after modafinil. The committee noted that the assumptions made in the economic model were highly sensitive to various factors.
