Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence indicates that sodium zirconium cyclosilicate lowers serum potassium levels, which is critical for treating hyperkalaemia. However, the clinical trials did not provide direct evidence comparing its effectiveness against standard care in the Healthcare, particularly for chronic hyperkalaemia. The trials primarily involved patients with lower potassium levels than those typically treated in the Healthcare, and the committee noted that the lack of robust comparative data limits the ability to claim superior clinical effectiveness.
Cost effectiveness
The cost-effectiveness estimates for sodium zirconium cyclosilicate suggest it is a good use of Healthcare resources, particularly for treating acute life-threatening hyperkalaemia. The ICERs were reported to be below £20,000 per QALY gained, indicating that it is clearly cost-effective under common thresholds, despite some uncertainties in the model.
Quality of life
While sodium zirconium cyclosilicate may allow patients to continue RAAS inhibitors, which could improve quality of life, there is no direct evidence from the trials showing that it improves HRQoL. The committee acknowledged that the treatment might help maintain RAAS inhibitors but did not find evidence that it directly enhances quality of life or extends life expectancy.
Supporting Domains
Safety and Adverse Effects
Sodium zirconium cyclosilicate has an acceptable safety profile, with the main adverse effect being hypokalaemia. The committee noted that while hypokalaemia can be serious, the treatment is less likely to cause it when used at higher serum potassium levels. Overall, the adverse effects reported were manageable and comparable to existing therapies.
Comparator Selection
The trials primarily compared sodium zirconium cyclosilicate to standard care but did not include a robust head-to-head comparison against the most relevant existing treatments for hyperkalaemia. The committee noted that the evidence was based on single-arm trials and lacked direct comparisons to standard care, which limits the strength of the conclusions.
Patient Population and Subgroups
The patient population in the trials included individuals with chronic kidney disease and heart failure, which are relevant subgroups for the intended use of sodium zirconium cyclosilicate. However, the committee noted that the population was narrower than the marketing authorisation, focusing on those with confirmed hyperkalaemia, which is appropriate for the treatment’s intended use.
Care Pathway Integration
Sodium zirconium cyclosilicate can be integrated into existing care pathways with minor adjustments. It is intended to be used alongside standard care for hyperkalaemia, which is already established in clinical practice. The committee noted that it complements existing treatments rather than requiring significant changes to the care pathway.
Resource Use and Cost Implications
The implementation of sodium zirconium cyclosilicate is expected to have a manageable budget impact, as it is associated with lower costs compared to existing treatments for hyperkalaemia. The committee concluded that it represents a cost-effective option for the Healthcare, particularly in emergency settings.
Evidence Quality and Robustness
The evidence base includes several trials, but there are significant limitations, including the lack of direct comparative data against standard care and reliance on single-arm studies. The committee noted that while the trials showed sodium zirconium cyclosilicate effectively lowers potassium levels, the overall robustness of the evidence is limited.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term benefits of sodium zirconium cyclosilicate, particularly concerning its impact on mortality and quality of life. The committee highlighted the need for further research to address these uncertainties, especially regarding the treatment’s effects on RAAS inhibitor use and long-term outcomes.
