Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Vadadustat demonstrated comparable efficacy to erythropoiesis stimulating agents (ESAs) in increasing hemoglobin levels, meeting non-inferiority criteria. However, the evidence indicates that vadadustat does not provide a clear advantage over ESAs, as shown by the trials where the primary efficacy outcome favored darbepoetin alfa, albeit within the non-inferiority margin.
Cost effectiveness
The cost-effectiveness analysis indicated that vadadustat is less effective and less costly than ESAs, with an ICER over £30,000 per QALY. This suggests low cost-effectiveness, requiring justification for its price relative to the benefits it provides.
Quality of life
The committee acknowledged that anaemia significantly impacts the quality of life for patients with chronic kidney disease (CKD). While specific HRQoL data for vadadustat was not detailed, the overall context suggests a moderate improvement in quality of life due to the treatment of symptomatic anaemia.
Supporting Domains
Safety and Adverse Effects
The safety profile of vadadustat was comparable to that of darbepoetin alfa, with no significant differences in major adverse cardiovascular events. This indicates an acceptable safety profile with manageable adverse effects.
Comparator Selection
The trials compared vadadustat directly with darbepoetin alfa, a standard treatment for symptomatic anaemia in CKD patients on dialysis. This direct comparison is appropriate and aligns with clinical practice.
Patient Population and Subgroups
The trials included a diverse population of patients with dialysis-dependent CKD, which enhances the generalizability of the findings. However, some subgroup analyses were limited, but the core population was well represented.
Care Pathway Integration
Vadadustat can be integrated into existing treatment pathways with minimal disruption, as it offers an oral alternative to injectable ESAs, which may be beneficial for patients with needle phobia.
Resource Use and Cost Implications
While vadadustat is less costly than ESAs, the overall resource implications are significant, and the treatment may not be sustainable at scale without careful budget management.
Evidence Quality and Robustness
The evidence base is supported by two large non-inferiority trials, which, despite some methodological concerns, provide a robust foundation for the evaluation of vadadustat.
Uncertainty, Sensitivity, and Broader Impacts
There is notable uncertainty regarding the long-term effectiveness and cost-effectiveness of vadadustat, particularly given the variability in ESA pricing and treatment discontinuation rates.
