Presentation (CTI)

OBJECTIVES: In heterogeneous populations, a new treatment with equivalent efficacy may still generate incremental responders compared to standard treatment(s). HTA evaluations typically assess value at the level of an average patient which cannot capture this additional value. We developed a disease-agnostic simulation framework to quantify this potential underestimation.
METHODS: A patient-level simulation estimated the incremental value of adding a new treatment to a formulary with one to four simulated existing options targeted to five pre-specified biomarker-defined disease processes. Biomarker levels were assumed to predict treatment response. Overall response rates were held constant so that no treatment was superior. Population heterogeneity was varied by changing the spread of biomarker distributions. The proportion of additional patients responding with the addition of a new treatment illustrated the population level incremental treatment benefit. We examined the impact of adding a new treatment when two to four therapies were already available under low, moderate, and high population heterogeneity.
RESULTS: Adding a new treatment to two existing options delivered the greatest proportion of incremental responders (3%, 15%, and 17% under low, moderate, and high heterogeneity, respectively). Increasing the number of available comparators reduced the incremental responders. Notably, even when adding a fifth treatment, 5% and 2% incremental responders were still estimated under high and moderate heterogeneity respectively with equivalent overall efficacy.
CONCLUSIONS: Incremental therapeutic value depends on population heterogeneity, treatment targeting, and formulary size. Our analysis suggests that novel treatments with equivalent overall efficacy can still generate substantial population-level health gains when heterogeneity is moderate or high, which standard patient-level cost-effectiveness analyses may miss. Future work could assess missed value in specific indications, and test different market sizes, heterogeneity levels and biomarker treatment specificity.