Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Ranibizumab demonstrated a clear clinical advantage over sham injection in both the BRAVO and CRUISE trials, with statistically significant improvements in best corrected visual acuity (BCVA) scores at 6 and 12 months. The average gain in BCVA was 18.3 letters in BRAVO and 14.9 letters in CRUISE, both significantly better than the sham groups. However, the exclusion of patients with significant retinal ischaemia limits the generalizability of these results.
Cost effectiveness
The base-case ICER for ranibizumab compared to best supportive care in CRVO was £8643 per QALY gained, which is defensible and within acceptable thresholds. The ICER for BRVO was higher but still considered acceptable under certain conditions, particularly when laser treatment is not an option.
Quality of life
The NEI VFQ-25 scores indicated significant improvements in quality of life for patients receiving ranibizumab compared to sham injection, with a statistically significant difference of 10.4 points at 6 months in BRAVO. This suggests strong evidence of quality-of-life benefits associated with treatment.
Supporting Domains
Safety and Adverse Effects
Ranibizumab has a favorable safety profile, with low rates of ocular adverse events compared to sham injection. The overall frequency of adverse effects was low, and the treatment was well tolerated, indicating a good safety profile.
Comparator Selection
The manufacturer did not provide direct evidence comparing ranibizumab with bevacizumab or dexamethasone, which are relevant comparators. While grid laser photocoagulation was used as a comparator, the lack of direct comparisons limits the robustness of the evidence.
Patient Population and Subgroups
The trials included a representative population of patients with visual impairment due to RVO, although most patients with significant retinal ischaemia were excluded. This limits the generalizability but still covers a significant portion of the intended patient population.
Care Pathway Integration
Ranibizumab can be integrated into existing care pathways with minimal disruption, as it is administered via intravitreal injection, which is already a common practice in ophthalmology. Minor adjustments may be needed for monitoring and follow-up.
Resource Use and Cost Implications
The economic model indicates that ranibizumab is likely to be a cost-effective option, particularly when considering the patient access scheme. The budget impact is manageable, aligning with Healthcare planning.
Evidence Quality and Robustness
The evidence base is supported by two robust RCTs (BRAVO and CRUISE) with low bias risk. However, the exclusion of certain patient populations and the reliance on indirect comparisons introduce some limitations.
Uncertainty, Sensitivity, and Broader Impacts
There are uncertainties regarding the long-term effectiveness and safety of ranibizumab, particularly in patients with retinal ischaemia. The economic model also has uncertainties related to assumptions about utility gains and mortality risks.
