Plain Language Summary

Sickle cell disease is a common genetic disorder affecting around 100,000 people in the United States, with significant impacts on quality of life and life expectancy, particularly within African American and Hispanic communities. Traditional treatments offer limited improvements, and the life expectancy for individuals with sickle cell disease remains much lower than average. Recently, two gene therapies, lovo-cel and exa-cel, have been approved, providing potential curative options for patients aged 12 and older. However, their cost-effectiveness has been uncertain.

This study explores the application of the Generalized Risk-Adjusted Cost-Effectiveness (GRACE) model to assess the societal value of curing sickle cell disease through these gene therapies. The GRACE model adjusts traditional cost-effectiveness analysis by incorporating factors like disease severity, treatment outcome uncertainty, and the trade-offs between life expectancy and quality of life. These adjustments provide a more comprehensive evaluation of the therapies' benefits.

The research recalibrated a previous assessment of lovo-cel and exa-cel using GRACE, leading to a 6% reduction in incremental cost-effectiveness ratios for both therapies. This means the incremental cost per quality-adjusted life year with both gene therapies decreased from $192,651 to $182,036 using a direct payer perspective and from $161,816 to $152,900 using a societal perspective. Furthermore, willingness-to-pay thresholds increased by approximately 50%, indicating a higher valuation of treatments under the GRACE framework. As a result, both therapies are considered cost-effective from direct payer and societal perspectives when using GRACE-adjusted estimates.

The GRACE model highlights the limitations of traditional cost-effectiveness analysis, which often fails to capture the full societal value of treatments for severe diseases like sickle cell disease. Traditional methods may not fully account for the impact on patients' ability to achieve life goals and the broader societal implications. By adopting GRACE, healthcare decision makers can facilitate broader acceptance of innovative therapies that significantly enhance patient quality of life.

For patients, lovo-cel and exa-cel offer promising improvements in health outcomes. Healthcare decision makers can use GRACE to make more informed resource allocation decisions, ensuring that treatments providing substantial societal value are recognized and funded. Researchers are encouraged to explore further applications of GRACE in evaluating healthcare technologies, particularly those targeting severe conditions.

In conclusion, implementing the GRACE model provides a more precise estimation of the societal value of gene therapies for sickle cell disease, supporting more efficient and equitable healthcare resource allocation. This case study serves as a roadmap for incorporating GRACE elements into health technology assessments, potentially transforming cost-effectiveness evaluations and healthcare decision making.

^{Note: This content was created with assistance from artificial intelligence (AI) and has been reviewed and edited by ISPOR staff. For more information or for inquiries on ISPOR’s AI policy, click here or contact us at info@ispor.org.}