Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Avatrombopag has shown comparable efficacy to existing TPO-RAs, meeting non-inferiority but lacking direct head-to-head evidence. The evidence primarily comes from Study 302, which indicates that avatrombopag is more effective than placebo in increasing platelet counts, but the indirect comparisons with other TPO-RAs introduce uncertainty.
Cost effectiveness
The cost-effectiveness estimates for avatrombopag are below what NICE typically considers acceptable, indicating a strong economic value. The company provided updated analyses that support its cost-effectiveness despite some uncertainties.
Quality of life
The evidence suggests that avatrombopag may improve quality of life by providing an oral treatment option without dietary restrictions, which is a significant advantage over other treatments. However, specific validated HRQoL data is limited.
Supporting Domains
Safety and Adverse Effects
Avatrombopag has a broadly similar incidence of adverse reactions compared to placebo, with no significant safety concerns raised in the trials. The safety profile appears acceptable, with manageable adverse events.
Comparator Selection
The comparators used in the analysis were appropriate as they included other TPO-RAs. However, the reliance on indirect comparisons raises some concerns about the robustness of the evidence.
Patient Population and Subgroups
The trial population may not fully represent the Healthcare population, with concerns about age and baseline characteristics. While the core population is covered, there are limitations in subgroup analyses.
Care Pathway Integration
Avatrombopag can be integrated into existing treatment pathways with minimal disruption, as it is an oral medication that does not require new infrastructure or significant changes in practice.
Resource Use and Cost Implications
The resource implications of implementing avatrombopag are manageable, and the economic model suggests that it is likely to be resource-efficient compared to existing treatments.
Evidence Quality and Robustness
While the evidence from Study 302 is robust, there are concerns regarding recruitment and attrition issues that limit the overall robustness of the evidence base. The reliance on a single pivotal trial adds to the uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties related to the clinical evidence and economic modeling assumptions, particularly regarding the treatment duration and response definitions. These uncertainties may impact the overall assessment.
