Presentation (CTI)

OBJECTIVES: Prioritizing symptomatic point changes on clinical outcomes unfairly discounts disease-modifying treatment effects, primarily because early prevention-like effects are minimized in favor of large, late treatment effects that only prolong the late, low-function stages of disease. Early intervention is often more effective in slowing disease progression, and prolongs the early, highly functional disease stages. We define clinical meaningfulness in terms of disease time savings and incremental cost savings, addressing this challenge.
METHODS: Estimates of progression in clinical trials of neurodegenerative treatments were used to demonstrate how different changes translate into time savings, at different stages of disease. Further, by aggregating costs across disease stages, cost savings can be calculated from disease time. Associating early treatment with prolonging a mild stage with better effects was modeled using simulations.
RESULTS: The large time and cost savings that correspond to traditional boundaries of symptomatic effect sizes with treatment are compared to annual and lifetime cost savings due to disease modification using total cost of disease over 10 years as the reference cost. Early intervention results in much larger cost savings than later intervention, when larger treatment effects are assumed in early disease.
Simulations indicate that disease modifying treatments given over 10 years save 2-4 times as much money as symptomatic therapies with cost savings of 80% of the total cost over the first 1-3 years of disease slowing treatment effects with larger slowing in early disease. Disease slowing by 50% on average corresponds to 80% time savings with 12 months of very early treatment, and 60% (10-year) cost reductions, which is more than the money saved with late symptomatic, preserving high functional performance.
CONCLUSIONS: Better treatment effects in earlier disease, consistent with disease modifying effects, result in pharmacoeconomic benefits that are self-aggregating, keeping individuals at slowly-progressive, easier-to-modify stages for a longer period of time.