OBJECTIVES: Cost-effectiveness analyses are often conducted to evaluate new medicines. However, there may be important limitations to standard cost-effectiveness methods when applied to lifelong treatments for rare, chronic, genetic diseases – particularly when projected survival benefits take years to materialize. We explore these limitations and quantify their impact in the context of treatment for cystic fibrosis (CF), a rare, chronic, debilitating genetic disease affecting 30,000 people in the US.

METHODS: A patient-level simulation was developed to assess the impact of initiating the CFTR modulator ivacaftor at age 2 years vs. best supportive care (BSC) on clinical outcomes, costs, and quality-adjusted life-years in CF patients with an indicated CFTR gating mutation. Model assumptions were varied to evaluate the impact on incremental cost-effectiveness ratios (ICERs): 1) discount rate (base-case: 3% costs and outcomes; alternate scenario (AS): 3% costs, 1.5% outcomes); 2) utility values (base-case: no treatment-specific utilities; AS: 0.1 ivacaftor-specific utility increment); 3) disease management costs (base-case: include disease management costs during extended survival; AS: exclude these costs); 4) introduction of generic treatment options (base-case: ivacaftor price constant over entire model horizon; AS: ivacaftor price reduction at patent expiry).

RESULTS: Initiating ivacaftor at age 2 years was projected to increase median survival by 26.0 years (47.4 for BSC vs. 73.4 for ivacaftor). Although the base-case ICER was $1,165,595, this estimate was highly sensitive to modeling assumptions. Applying the alternate assumptions reduced the ICER to $130,317. Application of differential discount rates alone reduced the base-case ICER by >50%.

CONCLUSIONS: These results highlight the unique challenges to modeling lifelong, life-extending therapies to treat chronic, genetic diseases. Several modeling assumptions penalize these types of medicines for keeping patients alive longer and providing benefits far in the future. Applying alternative assumptions to address these limitations reduced the ICER for ivacaftor by 89%.

Sponsored by Vertex Pharmaceuticals Incorporated.