Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence suggests that tixagevimab plus cilgavimab reduces SARS-CoV-2 infection compared to no treatment, but the studies were conducted early in the pandemic with different variants. Recent data indicate that the treatment is unlikely to prevent infection with most circulating variants, leading to a conclusion of unproven efficacy against current strains.
Cost effectiveness
The cost-effectiveness estimates for tixagevimab plus cilgavimab are highly uncertain and likely exceed acceptable thresholds for Healthcare resources. The committee concluded that the treatment is not cost-effective given the lack of evidence for its effectiveness against most variants.
Quality of life
While the treatment may provide some quality-of-life benefits by reducing anxiety related to COVID-19, the evidence is not robust. The committee noted that the utility gain from treatment was likely overestimated, and the actual benefit may be minimal given the uncertainty around efficacy.
Supporting Domains
Safety and Adverse Effects
The treatment has an acceptable safety profile with manageable adverse effects. There were no significant safety concerns raised in the evidence, and the adverse events reported were consistent with those expected for monoclonal antibodies.
Comparator Selection
The treatment was compared to no preventative treatment, which is acceptable. However, the lack of head-to-head comparisons against current standard treatments limits the robustness of the evidence.
Patient Population and Subgroups
The population studied included individuals at high risk of severe COVID-19, but there were concerns about the generalizability of the findings to the broader population. The committee noted significant heterogeneity within the eligible population.
Care Pathway Integration
The treatment can be integrated into existing healthcare pathways with minor adjustments. Administration is straightforward, and the treatment can be delivered in outpatient settings.
Resource Use and Cost Implications
The treatment poses a significant resource burden, particularly given the uncertainty around its effectiveness and the high costs associated with administration. The committee expressed concerns about the affordability of the treatment at scale.
Evidence Quality and Robustness
The evidence base includes a Phase 3 trial, but there are significant limitations regarding the applicability of the results to current variants. Observational studies also raised concerns about generalizability and potential biases.
Uncertainty, Sensitivity, and Broader Impacts
There is substantial uncertainty regarding the treatment’s effectiveness against current variants, which raises concerns about its broader impacts on public health and resource allocation. The committee noted the need for further research to address these uncertainties.
