Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the GWPCARE6 trial indicates that cannabidiol significantly reduces seizure frequency and increases the number of seizure-free days compared to placebo. Specifically, there was a statistically significant 30% reduction in seizures and a notable increase in seizure-free days, which supports a clear clinical advantage over standard care. However, the lack of Phase 3 evidence limits the rating to A+.
Cost effectiveness
The cost-effectiveness estimates for cannabidiol are uncertain, with the ERG indicating an ICER above £30,000 per QALY gained, which is considered low cost-effectiveness. The committee acknowledged the uncertainties in the economic model, which affects the overall value proposition of the treatment.
Quality of life
While the trial did not show a direct association between seizure reduction and improved quality of life, clinical experts indicated that fewer seizures generally lead to better daily functioning and mental health. The evidence suggests moderate improvements in HRQoL, but the lack of robust data linking seizure control to quality of life outcomes prevents a higher rating.
Supporting Domains
Safety and Adverse Effects
Cannabidiol has a manageable safety profile with mostly mild adverse effects such as diarrhea and decreased appetite. Clinical experts noted that while adverse events are common, they are generally tolerable, supporting a very good safety rating.
Comparator Selection
The comparator for cannabidiol was appropriately selected as usual care, which includes antiseizure medications and other interventions. This reflects a good alignment with clinical practice, although there were some concerns regarding the specific population definitions.
Patient Population and Subgroups
The trial population is broadly generalizable to the Healthcare clinical practice, including a range of ages and conditions. However, there are minor gaps in subgroup analyses that prevent a top-tier rating.
Care Pathway Integration
Cannabidiol can be integrated into existing care pathways with minor adjustments, such as monitoring and potential dose adjustments of concurrent medications. This indicates a good fit within current clinical practices.
Resource Use and Cost Implications
The economic model indicates a high resource burden, with uncertainties around hospitalisation rates and healthcare resource use. This raises concerns about the sustainability of the budget impact, leading to a B++ rating.
Evidence Quality and Robustness
The evidence base is primarily derived from a well-conducted RCT (GWPCARE6), although there are some methodological concerns and uncertainties in the economic model. Overall, the evidence is acceptable but not without limitations.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties in the cost-effectiveness model and the assumptions made regarding the treatment’s benefits. This high level of uncertainty, combined with the potential for negative externalities, leads to a B+ rating.
