A Comparison of Generalized Risk Adjusted Cost-Effectiveness Analysis (GRACE) vs Traditional Cost-Effective Analysis (CEA) Estimates for the Treatment of Early-Onset Metachromatic Leukodystrophy (MLD)

Speaker(s)

Ortega L1, Incerti D1, Bean K2, Fields C3, Pang F4, Lakdawalla D5
1EntityRisk, Inc., Washington, DC, USA, 2Orchard Therapeutics, Hook, HAM, UK, 3Orchard Therapeutics, London, UK, 4Orchard Therapeutics, London, LON, UK, 5USC Leonard D. Schaeffer Center for Health Policy and Economics, Los Angeles, CA, USA

Presentation Documents

OBJECTIVES: MLD is an ultra-rare, rapidly progressive neurodegenerative disease leading to motor and cognitive decline and premature death. This study aimed to compare cost-effectiveness estimates from traditional CEA to those produced by GRACE for arsa-cel vs. best supportive care (BSC) for the treatment of early-onset MLD. GRACE generalizes traditional CEA by accommodating any empirically valid utility function over health-related quality-of-life (HRQoL).

METHODS: Traditional CEA and GRACE models were estimated for a combined MLD cohort encompassing pre-symptomatic late infantile and early juvenile patients, along with early symptomatic early juvenile patients. Estimates from Mulligan et al. (2024) were used to parameterize expo-power and constant relative risk aversion (CRRA) GRACE utility functions over health. Additional analyses adjusted for the effect of pre-existing disability on willingness to pay for health. Non-negative HRQoL values proposed by ICER during its appraisal of arsa-cel were used in the analysis.

RESULTS: In the scenario of the combined MLD cohort without disability adjustment, the traditional CEA model yielded an ICER of $123,247 per QALY, with an incremental gain of 19.13 QALYs. GRACE produced an ICER of $122,273 per QALY with an incremental gain of 19.29 QALYs. Similar results were found when considering alternative scenarios such as estimating GRACE using a CRRA utility function and when adjusting for disability.

CONCLUSIONS: This is one of the first applications of GRACE to an ultra-rare disease. In this instance, incremental QALYs and the cost-effectiveness estimates from the GRACE analysis were similar to those generated from traditional CEA after exploring several scenarios. The results suggest that economic valuations of arsa-cel are robust to generalizations of utility over quality of life beyond what is permitted by traditional CEA. A future scenario will investigate the impact of negative HRQoL values.

Code

EE102

Topic

Economic Evaluation

Topic Subcategory

Cost-comparison, Effectiveness, Utility, Benefit Analysis

Disease

Genetic, Regenerative & Curative Therapies, Pediatrics, Rare & Orphan Diseases