Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the MEAD trials demonstrates that dexamethasone intravitreal implant is more effective than a sham procedure, which serves as a proxy for continued anti-VEGF therapies. The trials showed significant improvements in best-corrected visual acuity (BCVA) at 39 months, indicating a clear clinical advantage over existing treatments. However, the absence of direct evidence for the specific subgroup of patients for whom non-corticosteroids are unsuitable slightly limits the strength of the evidence.
Cost effectiveness
The cost-effectiveness analysis indicates that dexamethasone intravitreal implant is likely to be cost-effective compared to anti-VEGF therapies, with ICERs showing that it dominates these comparators. The committee concluded that it represents a cost-effective use of Healthcare resources, particularly when considering the net monetary benefit approach.
Quality of life
The patient expert testimony highlighted that reducing the frequency of eye injections would significantly improve quality of life for patients with diabetic macular oedema. The potential for fewer hospital visits and injections is expected to enhance overall well-being, although specific validated HRQoL data were not presented.
Supporting Domains
Safety and Adverse Effects
The safety profile of dexamethasone intravitreal implant appears acceptable, with manageable adverse events reported. The committee noted that the treatment is used in small quantities directly into the eye, which minimizes systemic side effects. However, some concerns regarding the long-term safety profile remain.
Comparator Selection
The company appropriately selected anti-VEGF therapies as the main comparators for patients who do not respond to non-corticosteroids. The committee accepted that these are the most relevant comparators, although the exclusion of other potential comparators like laser therapy was justified based on clinical practice.
Patient Population and Subgroups
The trial population is generally representative of the intended patient population, particularly for those with a phakic lens. However, there are limitations in subgroup analyses for patients who cannot receive non-corticosteroids, which slightly affects the generalizability of the findings.
Care Pathway Integration
Dexamethasone intravitreal implant can be integrated into existing care pathways with minor adjustments. The treatment reduces the frequency of hospital visits, which aligns well with current clinical practices and addresses capacity issues in the Healthcare.
Resource Use and Cost Implications
The implementation of dexamethasone intravitreal implant is expected to have a manageable budget impact, with potential cost savings due to reduced treatment frequency. However, the overall resource burden is notable, which could raise concerns if the treatment is adopted widely.
Evidence Quality and Robustness
The evidence base is primarily derived from two Phase 3 RCTs, which are robust in design. However, the reliance on a sham comparator and the absence of evidence for a specific subgroup introduce some methodological concerns.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the long-term outcomes and the specific subgroup of patients, the overall context of unmet need and the potential benefits of the treatment mitigate these concerns. The committee noted that the risk to the Healthcare is low.
