Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the PACIFIC trial demonstrates a clear clinical advantage for durvalumab, showing significant improvements in both progression-free survival (24.9 months vs. 5.5 months) and overall survival (63.1 months vs. 29.6 months) compared to standard care. The hazard ratios of 0.47 for progression-free survival and 0.61 for overall survival indicate substantial benefits, supporting the rating of A+.
Cost effectiveness
The cost-effectiveness estimates for durvalumab are reported to be between £20,000 and £30,000 per QALY gained, which is within the acceptable range for Healthcare resources. This indicates that durvalumab is marginally cost-effective, supporting an A rating.
Quality of life
While the document does not provide extensive HRQoL data, it mentions that durvalumab has improved quality of life for patients, particularly in terms of survival benefits and symptom management. This suggests moderate improvements in HRQoL, justifying an A rating.
Supporting Domains
Safety and Adverse Effects
The safety profile of durvalumab is described as very good, with mostly mild or moderate adverse events. The document indicates that serious adverse events are rare, which supports a rating of A+ for safety.
Comparator Selection
Durvalumab was compared against standard care, which is appropriate for the patient population. The committee recognized standard care as routine surveillance and annual CT scans, making the comparator selection strong and justifying an A+ rating.
Patient Population and Subgroups
The trial population is largely representative of the intended patient population, particularly those with PD-L1 expression of 1% or more. However, there are some limitations regarding the generalizability to patients with unknown PD-L1 status, justifying an A rating.
Care Pathway Integration
Durvalumab can be integrated into existing care pathways with minor adjustments, as it has become standard care in the Healthcare for this indication. This ease of integration supports an A+ rating.
Resource Use and Cost Implications
The budget impact is manageable, and the economic model suggests that durvalumab is a cost-effective option. The committee’s conclusion that the ICERs are within acceptable limits supports an A rating.
Evidence Quality and Robustness
The evidence is primarily derived from the PACIFIC trial, which is a robust RCT. While there are some concerns regarding the extrapolation of data, the overall quality of evidence is strong, justifying an A rating.
Uncertainty, Sensitivity, and Broader Impacts
There are areas of uncertainty regarding the generalizability of the PACIFIC trial and the assumptions made in the economic model. While the committee acknowledged these uncertainties, they deemed the overall impact on decision-making to be manageable, justifying a B++ rating.
