What payers will ask
Is the clinical benefit the kind payers reward? — Clinical effectiveness
The clinical evidence from the BOSTON trial indicates that selinexor combination increases progression-free survival compared to bortezomib plus dexamethasone at second line, but does not show a significant improvement in overall survival. The trial was not statistically powered to detect differences in outcomes in the subgroups, and indirect comparisons with other treatments suggest no clear advantage. Therefore, while there is some evidence of comparable efficacy, it does not demonstrate a clear edge over existing options.
Does the economic case hold at the expected price? — Cost effectiveness
The cost-effectiveness estimates for selinexor combination compared with carfilzomib plus dexamethasone are within acceptable ranges, but the estimates for third-line use compared with ixazomib combination exceed NICE’s thresholds. This indicates a low cost-effectiveness overall, requiring justification for its price.
Is there quality-of-life evidence payers weigh? — Quality of life
The document indicates that the treatment has gastrointestinal side effects, which may impact quality of life. Although there are mentions of potential benefits for caregivers, the overall evidence on HRQoL improvements is limited and does not show significant gains compared to standard care.
Does the safety profile hold up for payers? — Safety and Adverse Effects
The safety profile of selinexor combination is acceptable, with manageable adverse events primarily being gastrointestinal. The document notes that dose reductions can mitigate some side effects, indicating a good tolerability overall.
Was the drug compared against what payers expect? — Comparator Selection
The primary comparator used in the clinical trial (bortezomib plus dexamethasone) is not considered relevant for second or third-line treatment. While indirect comparisons were made with other treatments, the lack of direct evidence against the most relevant comparators raises concerns about the appropriateness of the selected comparators.
Is the population defined the way payers need it? — Patient Population and Subgroups
The trial population in BOSTON included patients who may not fully represent the typical Healthcare population, particularly regarding prior treatments. The committee noted that many participants had not previously received lenalidomide, which is a common treatment in practice, leading to concerns about generalizability.
Does the drug fit how care is delivered and paid for? — Care Pathway Integration
Selinexor is an oral treatment, which facilitates easier administration compared to intravenous options. The committee acknowledged that it fits well into existing care pathways, requiring only minor adjustments.
Are the wider system costs understood? — Resource Use and Cost Implications
The economic model indicates a high resource burden, particularly in the context of subsequent treatment costs. The committee expressed concerns about the sustainability of the budget impact, especially given the uncertainty surrounding the cost-effectiveness estimates.
Would the evidence survive payer scrutiny? — Evidence Quality and Robustness
The evidence base is primarily derived from a Phase 3 trial (BOSTON), which is robust but has limitations regarding statistical power and generalizability. The committee noted methodological concerns but acknowledged the overall strength of the evidence.
How exposed is the case to uncertainty? — Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the generalizability of the trial results and the long-term effectiveness of the treatment. The committee highlighted the need for caution in interpreting the cost-effectiveness estimates due to these uncertainties.
