Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for pralsetinib suggests it could be clinically effective, but the benefit is uncertain due to the lack of direct comparisons with standard treatments. The evidence comes from a single-arm study, which limits the ability to draw definitive conclusions about its efficacy compared to existing options.
Cost effectiveness
The cost-effectiveness estimates for pralsetinib are uncertain and considered too high for it to be deemed a cost-effective use of Healthcare resources. The committee noted that the maximum acceptable ICER would be at the lower end of the range typically considered acceptable, indicating significant cost concerns.
Quality of life
There is no specific data presented on HRQoL improvements associated with pralsetinib. The document indicates that the treatment may help manage symptoms of advanced NSCLC, but without robust evidence, the impact on quality of life remains unclear.
Supporting Domains
Safety and Adverse Effects
Pralsetinib is described as having a manageable safety profile, with adverse events that are consistent with those seen in similar treatments. The document does not indicate any severe safety concerns that would undermine its use.
Comparator Selection
The comparators used in the appraisal were aligned with Healthcare practice, but the company did not compare pralsetinib directly with all relevant standard treatments. This limits the robustness of the comparative effectiveness data.
Patient Population and Subgroups
The patient population considered in the trials reflects the intended real-world population for pralsetinib, with appropriate subgroup analyses for untreated and previously treated patients. However, the lack of data for squamous NSCLC is a limitation.
Care Pathway Integration
Pralsetinib is an oral treatment that offers a clear advantage over intravenous therapies typically administered in hospitals. This suggests a good fit within existing care pathways, although some adjustments may be necessary for RET fusion testing.
Resource Use and Cost Implications
The document indicates that the cost implications of pralsetinib are significant, and while it may provide some benefits, the overall resource burden raises concerns about its affordability within the Healthcare.
Evidence Quality and Robustness
The evidence base is primarily derived from a single-arm trial, which raises concerns about its robustness. The quality of the trial was marked down in several areas, indicating potential biases and limitations in the evidence.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the clinical effectiveness and cost-effectiveness of pralsetinib, particularly due to the reliance on indirect treatment comparisons and the assumptions made in the economic model.
