Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the SOLSTICE trial indicates that maribavir achieves a viral clearance rate of 55.7% compared to 23.9% for the investigator-assigned treatments (IAT), with a statistically significant difference (p<0.001). However, concerns about the trial's design, including potential biases and the generalizability of results, limit the confidence in these findings.
Cost effectiveness
The most plausible ICER for maribavir is around £20,000 per QALY gained, which is within the acceptable range for Healthcare resources. The committee acknowledged uncertainties in the cost-effectiveness estimates but concluded they were likely acceptable given the limited treatment options available.
Quality of life
The evidence suggests that maribavir may improve quality of life by allowing treatment at home, reducing the need for hospital visits, and potentially alleviating the psychological burden associated with CMV reactivation. However, specific HRQoL data from validated instruments is not extensively detailed in the document.
Supporting Domains
Safety and Adverse Effects
Maribavir has a favorable safety profile compared to existing treatments, with manageable adverse effects. The document notes that current treatments can cause significant side effects, making maribavir a preferable option for patients with refractory CMV infections.
Comparator Selection
The SOLSTICE trial compared maribavir to a range of investigator-assigned treatments, which included both monotherapy and combination therapy. While this is a reasonable approach, the variability in comparator treatments raises concerns about the robustness of the findings.
Patient Population and Subgroups
The trial population included patients who had undergone HSCT or SOT, but there are concerns regarding the representativeness of the sample and the generalizability of the results to the broader patient population, particularly due to imbalances in baseline characteristics.
Care Pathway Integration
Maribavir’s oral administration allows for treatment at home, which aligns well with current care pathways and reduces the need for hospital visits. This integration is seen as beneficial for patient management and recovery.
Resource Use and Cost Implications
The economic model suggests that maribavir is likely to be resource-efficient, particularly given the potential for reduced hospitalizations and the associated costs of current treatments. The committee noted that the budget impact is manageable.
Evidence Quality and Robustness
While the SOLSTICE trial provides Phase 3 evidence, concerns about trial design, potential biases, and missing data limit the robustness of the evidence. The committee noted these gaps but acknowledged the trial’s overall contribution to the evidence base.
Uncertainty, Sensitivity, and Broader Impacts
The committee recognized uncertainties in the clinical and economic evidence but noted that the treatment addresses a significant unmet need in a vulnerable patient population, which supports its use despite these uncertainties.
