Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence suggests that pitolisant hydrochloride reduces excessive daytime sleepiness, with and without CPAP. However, the committee noted uncertainty about the evidence due to the trial design and the lack of significant improvement in quality of life measures. The trials showed a reduction in ESS scores, but the overall efficacy compared to existing treatments remains comparable without a clear edge.
Cost effectiveness
The cost-effectiveness estimates for pitolisant hydrochloride are likely above what NICE considers acceptable. The ICERs presented were £32,430 and £28,431 per QALY gained, which the committee concluded were likely to be higher than acceptable thresholds, indicating poor value for the Healthcare.
Quality of life
The evidence regarding HRQoL improvements is mixed. While there was some improvement in the pain and discomfort dimension of the EQ-5D in one trial, there was no statistically significant difference in overall quality of life measures during the double-blind phase. This indicates a lack of robust evidence for meaningful HRQoL gains.
Supporting Domains
Safety and Adverse Effects
The safety profile of pitolisant hydrochloride appears acceptable, with no significant concerns raised regarding adverse effects in the trials. The committee noted that the follow-up period in related studies was sufficient to understand side effects, indicating a good tolerability profile.
Comparator Selection
The trials compared pitolisant hydrochloride against placebo and standard care, which is acceptable but does not include head-to-head comparisons with all key alternatives. This limits the robustness of the evidence regarding its comparative effectiveness.
Patient Population and Subgroups
The HAROSA trials included a diverse patient population, although there were some exclusions related to psychiatric conditions. The committee acknowledged that while the trials were broadly generalizable, they may under-represent individuals with psychiatric illnesses, which could affect the applicability of the results.
Care Pathway Integration
Pitolisant hydrochloride is likely to be integrated into existing care pathways with minor adjustments, primarily in secondary care settings. The committee noted that additional monitoring would be required, but overall integration appears manageable.
Resource Use and Cost Implications
The economic model indicates a high resource burden, with ICERs suggesting that the treatment may require restrictions due to its cost implications. The committee expressed concerns about the affordability of pitolisant hydrochloride within the Healthcare.
Evidence Quality and Robustness
While the evidence base includes randomized trials, there are significant limitations in the economic model and uncertainties in the clinical data. The committee noted gaps in the evidence that require further data to support robust conclusions.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the cost-effectiveness and clinical effectiveness of pitolisant hydrochloride, particularly related to the economic model and the assumptions made. The committee highlighted that these uncertainties could restrict its use.
