Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Dapagliflozin shows moderate benefit over standard care, with evidence from the DAPA-CKD trial indicating a significant reduction in the primary composite outcome of sustained eGFR decline, end-stage renal disease, or death from renal or cardiovascular causes (HR 0.61). However, the evidence does not cover all populations included in the marketing authorization, particularly those without type 2 diabetes or with lower eGFR levels.
Cost effectiveness
Dapagliflozin is considered cost-effective, particularly in the subgroup with a uACR of 22.6 mg/mmol or more, where it dominated standard care. The ICER for the subgroup with type 2 diabetes and a uACR of less than 22.6 mg/mmol was around £6,000 per QALY gained, which is well within NICE’s acceptable thresholds.
Quality of life
The committee noted that chronic kidney disease significantly impacts quality of life, and dapagliflozin is expected to improve this by delaying disease progression. While specific HRQoL data were not detailed, the overall benefits of slowing CKD progression suggest moderate improvements in patient well-being.
Supporting Domains
Safety and Adverse Effects
The adverse event profile of dapagliflozin is consistent with other indications, showing fewer serious adverse events compared to placebo. There were no cases of diabetic ketoacidosis, and the overall safety profile is favorable, indicating very good tolerability.
Comparator Selection
The company appropriately compared dapagliflozin plus standard care against standard care alone, which is the current best practice for CKD management. The inclusion of canagliflozin as a relevant comparator for certain subgroups further supports the robustness of the comparator selection.
Patient Population and Subgroups
While the DAPA-CKD trial included a representative population, there are significant gaps in evidence for patients without type 2 diabetes and those with lower eGFR levels. The committee acknowledged the need for further trials to address these gaps.
Care Pathway Integration
Dapagliflozin can be integrated into existing care pathways with minimal adjustments, primarily as an add-on to standard care involving ACE inhibitors or ARBs. This aligns with current clinical practices and guidelines.
Resource Use and Cost Implications
The budget impact of dapagliflozin is manageable, particularly given its cost-effectiveness in the recommended populations. The committee noted that while there may be a significant impact on Healthcare resources, the overall economic implications are justifiable.
Evidence Quality and Robustness
The evidence base is primarily supported by the DAPA-CKD trial, which is a robust Phase III RCT. However, there are some methodological concerns regarding the applicability of results to all patient populations, particularly those excluded from the trial.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the effectiveness of dapagliflozin in certain subgroups, particularly those without type 2 diabetes and with lower uACR levels. The committee recognized these uncertainties but noted the potential for significant benefits in the broader CKD population.
