Implementing the Generalized Risk-Adjusted Cost-Effectiveness (GRACE) Model for Sickle Cell Disease (SCD) - A Case Study.

Objectives: This study aims to quantify the societal value of curing sickle cell disease (SCD) by implementing the Generalized Risk-Adjusted Cost-Effectiveness (GRACE) method, thereby adjusting for factors such as disease severity, reduction of uncertainty in treatment outcomes, and trade-offs between quality of life (QoL) and life expectancy (LE) in a cost-effectiveness analysis (CEA).

Methods: Using GRACE, we recalibrated a recent health technology assessment (HTA) in SCD for two gene therapies, lovo-cel and exa-cel. The GRACE framework modified existing CEA by adjusting willingness to pay (WTP) thresholds based on untreated illness severity, incorporating treatment outcome uncertainty, and varying the substitution rates between LE and QoL across health states.

Results: Implementing the GRACE framework resulted in a 6% reduction in both direct and societal incremental cost-effectiveness ratios (ICERs) for lovo-cel and exa-cel, demonstrating a decrease from $192,651 and $161,816 to $182,036 and $152,900 per quality-adjusted life year, respectively. Additionally, WTP thresholds increased by approximately 50%, reflecting a higher valuation of treatments under GRACE. GRACE-adjusted estimates suggest lovo-cel and exa-cel are cost-effective from both direct payer and societal perspectives.

Conclusions: The GRACE method offers a more comprehensive and precise estimation of societal value, leading to more efficient and equitable resource allocation. This study not only highlights the limitations of traditional CEA in capturing the total societal value of treatments for severe diseases, but also provides a roadmap for incorporating GRACE model elements into HTAs, thereby facilitating broader acceptance of innovative therapies that significantly enhance patient QoL.