Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the TAGS phase 3 trial indicates that trifluridine-tipiracil provides a clear survival advantage over best supportive care, with the committee concluding that it improves overall survival. The most plausible ICER is less than £30,000 per QALY gained, which is within acceptable thresholds for Healthcare resources.
Cost effectiveness
The cost-effectiveness analysis shows that trifluridine-tipiracil is clearly cost-effective under common thresholds, with an ICER of £29,347 per QALY gained, which is defensible and aligns with NICE’s acceptable use of Healthcare resources.
Quality of life
The treatment is expected to improve quality of life by providing an oral option that minimizes hospital visits, which is significant for patients with metastatic gastric cancer. However, the evidence for HRQoL improvements is not robustly quantified in the model.
Supporting Domains
Safety and Adverse Effects
Trifluridine-tipiracil has an acceptable safety profile, with manageable adverse events such as neutropenia and anemia. While these side effects are notable, they are consistent with the expected tolerability for cancer treatments.
Comparator Selection
The treatment was compared against best supportive care, which is the most appropriate comparator for patients who have undergone multiple prior treatments. The committee concluded that this comparison is relevant and reflects current clinical practice.
Patient Population and Subgroups
The trial population is moderately representative of the intended patient population, though there are some concerns regarding the generalizability of the subgroup analyses due to the inclusion of patients from Japan and those with varying treatment histories.
Care Pathway Integration
Trifluridine-tipiracil can be integrated into existing care pathways with minor adjustments, as it is an oral treatment that does not require extensive changes to current practices, making it a feasible option for patients.
Resource Use and Cost Implications
The budget impact is manageable, and the treatment is expected to provide significant benefits relative to its costs, aligning with the Healthcare’s resource allocation strategies.
Evidence Quality and Robustness
The evidence is based on a phase 3 RCT, which is a strong design, although there are some limitations regarding the generalizability of the findings due to the trial population’s characteristics.
Uncertainty, Sensitivity, and Broader Impacts
While there is some uncertainty regarding the long-term outcomes and the generalizability of the trial results, the context of unmet need for treatment options in this patient population mitigates some of these concerns.
