What payers will ask
Is the clinical benefit the kind payers reward? — Clinical effectiveness
The clinical effectiveness of pembrolizumab is based on response rates and progression-free survival data from the KEYNOTE-087 trial. However, there is no direct evidence comparing pembrolizumab with current standard care, and the overall survival data is not mature. The committee noted that while pembrolizumab shows a beneficial effect on progression-free survival, the uncertainty regarding overall survival limits the strength of the evidence.
Does the economic case hold at the expected price? — Cost effectiveness
The cost-effectiveness estimates for pembrolizumab are highly uncertain, with ICERs ranging significantly based on different models. The committee concluded that the ICERs for both populations are too uncertain to recommend pembrolizumab for routine use, indicating a need for further data collection to clarify its economic value.
Is there quality-of-life evidence payers weigh? — Quality of life
There is limited data on HRQoL specifically related to pembrolizumab. The committee noted that utility values were derived from the KEYNOTE-087 trial, but there is considerable uncertainty regarding the utility decrease when disease progresses. The lack of comprehensive HRQoL data limits the ability to assess the treatment’s impact on patients’ overall well-being.
Does the safety profile hold up for payers? — Safety and Adverse Effects
Pembrolizumab has an acceptable safety profile, with adverse events primarily being manageable. The committee noted that while there are some concerns regarding adverse effects, they are not significant enough to undermine the overall value of the treatment.
Was the drug compared against what payers expect? — Comparator Selection
The comparator data primarily relied on the Cheah et al. study, which may not fully represent current standard care practices in the UK. The committee acknowledged that while this study was the best available evidence, it had limitations in terms of population representation and did not include best supportive care comparisons.
Is the population defined the way payers need it? — Patient Population and Subgroups
The trial populations for pembrolizumab are reasonably representative of the intended patient population, particularly for those who are transplant-ineligible. However, there are some limitations in subgroup analyses, particularly regarding the population that has had autologous stem cell transplant.
Does the drug fit how care is delivered and paid for? — Care Pathway Integration
Pembrolizumab can be integrated into existing care pathways with minor adjustments, such as additional monitoring for adverse effects. The committee noted that the treatment does not require significant changes to current clinical practices.
Are the wider system costs understood? — Resource Use and Cost Implications
The resource implications of pembrolizumab are significant, with concerns raised about the overall budget impact. The committee noted that while the treatment may provide benefits, the high costs associated with it raise concerns about affordability and sustainability.
Would the evidence survive payer scrutiny? — Evidence Quality and Robustness
The evidence base for pembrolizumab includes data from a single-arm trial, which presents limitations in robustness and generalizability. The committee noted that while the trial provides some insights, the lack of direct comparative data introduces uncertainty.
How exposed is the case to uncertainty? — Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty surrounding the cost-effectiveness estimates and the long-term outcomes of pembrolizumab. The committee highlighted that the assumptions made in the economic models introduce significant variability in the results, which could impact decision-making.
