OBJECTIVES: The Institute for Clinical and Economic Review (ICER) recently announced that it will explore pilot testing the Generalized Risk-Adjusted Cost‑Effectiveness (GRACE) framework in their cost-effectiveness analyses (CEAs), suggesting a willingness to account for individual and/or societal value judgments related to risk aversion and disease severity. Recent empirical research suggests that traditional CEAs undervalue treatments for severe diseases. To investigate this further, we applied the GRACE framework to an existing CEA on two gene therapies for sickle cell disease (SCD).

METHODS: To estimate the GRACE results, we applied the published stepwise approach for using GRACE to the traditional cost‑effectiveness outcomes for lovo­‑cel and exa‑cel in SCD. For that we used the marginal rate of substitution (MRS), the willingness-to-pay (WTP) GRACE parameters, and the certainty equivalence ratio for outcomes from the literature. Utilizing GRACE, the CEA for SCD changes in three substantive ways: 1) the WTP increases with untreated disease severity, 2) the average treatment effectiveness decreases with uncertainty in outcomes, and 3) the MRS between life expectancy and quality of life changes with health state utility after treatment.

RESULTS: In the traditional CEA, the cost per quality-adjusted life year (QALY) gained was $320,000 for lovo‑cel and $191,000 for exa‑cel. After implementing GRACE, these results lowered to $303,000 for lovo-cel and the $154,000 for exa‑cel. In the traditional CEA, lovo‑cel and exa­‑­cel had a value‑based price (VBP) of $1.7M at a threshold of $150,000 per QALY, while the VBP after the GRACE adjustment was $2.1M for both.

CONCLUSIONS: This case study in SCD demonstrates how traditional CEA methods may overlook sources of societal value that are quantitatively significant. By applying the GRACE method, health technology assessments can lead to more comprehensive and precise estimates of societal value thereby facilitating more efficient resource allocation.