Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Pembrolizumab shows moderate benefit over current care, with a 64% overall response rate in the KEYNOTE-087 trial and promising survival data. However, the overall survival data is not mature, and the evidence relies on indirect comparisons, which introduces uncertainty.
Cost effectiveness
The cost-effectiveness estimates for pembrolizumab are below £20,000 per QALY gained, which is considered acceptable by NICE. The committee noted that the most plausible ICERs were within acceptable thresholds for Healthcare resources.
Quality of life
The evidence indicates moderate improvements in HRQoL, with patient experts noting the importance of coping with the disease. However, the utility values are derived from limited data and may not fully capture the long-term impact on quality of life.
Supporting Domains
Safety and Adverse Effects
Pembrolizumab has a very good safety profile, with mostly mild to moderate adverse events reported. Serious adverse events are rare, indicating a favorable tolerability compared to existing therapies.
Comparator Selection
The evidence does not include direct comparisons with standard care, relying instead on indirect comparisons. While these suggest pembrolizumab may improve survival, the lack of direct evidence limits the robustness of the findings.
Patient Population and Subgroups
The trial population is broadly representative of the intended patient population, with relevant subgroup analyses. However, there are some concerns regarding the severity of disease in the real-world data compared to trial participants.
Care Pathway Integration
Pembrolizumab can be integrated into existing care pathways with minor adjustments. It serves as a bridge to stem cell transplant, fitting well into the treatment sequence for patients who cannot undergo ASCT.
Resource Use and Cost Implications
The resource implications are manageable, with the potential for cost savings due to the effectiveness of pembrolizumab as a treatment option. The economic model indicates a reasonable budget impact.
Evidence Quality and Robustness
The evidence base includes data from both clinical trials and real-world settings, although there are some methodological concerns and reliance on indirect comparisons that introduce uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty surrounding the indirect comparisons and the economic model structure. The committee noted that while the ICER is acceptable, the high uncertainty in treatment effect estimates could impact decision-making.
