THE IMPACT OF GENERALIZED RISK ADJUSTED COST-EFFECTIVENESS ANALYSIS (GRACE) ON VALUE ASSESSMENT: FROM FORMAL ADOPTION TO GLOBAL METHODOLOGICAL TRENDS
Author(s)
Yunni Yi, PhD, MSc1, Anne Meiwald, MSc, BSc1, Louise Heron, MA, MSc1, Alex Hirst, BSc, MSc2;
1Adelphi Values PROVE, Bollington, United Kingdom, 2Adelphi Values PROVE, Senior Director, Bollington, United Kingdom
1Adelphi Values PROVE, Bollington, United Kingdom, 2Adelphi Values PROVE, Senior Director, Bollington, United Kingdom
OBJECTIVES: The GRACE framework extends traditional cost-effectiveness analysis (CEA) to better reflect societal value regarding disease severity and risk-aversion. This study examines GRACE application status, its impact on value assessment, and integration of its core principles in global HTA frameworks.
METHODS: A review of HTA websites, PubMed, and ISPOR proceedings (2020-2026) was conducted. Data were extracted from primary studies applying GRACE to identify its impact on incremental cost effectiveness ratios (ICERs) and willingness-to-pay (WTP) thresholds. Current methodological guidelines from major HTA bodies were analyzed for GRACE alignment.
RESULTS: ICER (US) remains the primary formal adopter, integrating GRACE into its "Value Assessment Framework" for severe diseases. Five applications were identified: sickle cell disease (SCD), non-small cell lung cancer (NSCLC), Hepatitis C, and neurology. In SCD and NSCLC, GRACE increased WTP thresholds by ~50% and reduced ICERs by 7-13% respectively. In Hepatitis C, incorporating "insurance value" reduced ICERs by over 90%. In neurology, net monetary benefit increased by 11.6% through better valuing of disability prevention. Aggregate analysis of 69 drugs across 53 diseases demonstrated GRACE is budget-neutral, redistributing value from mild to severe conditions. GRACE principles increasingly appear in international HTA: NICE (UK) implemented 2026 threshold updates to £25,000-£35,000/QALY with "Severity Modifiers," while CADTH (Canada) and EU Member States shifted toward "Unmet Medical Need" weightings prioritizing severe health shortfalls.
CONCLUSIONS: GRACE systematically corrects undervaluation of treatments for severe conditions. Formal adoption by ICER and emergence of severity modifiers globally signal a significant shift from "flat" QALYs toward risk-adjusted models. While challenges exist regarding empirical estimation of risk-aversion parameters and measurement of untreated health baselines, the adoption of GRACE like method by major HTA bodies is a critical step toward more consistent and equitable healthcare resource allocation.
METHODS: A review of HTA websites, PubMed, and ISPOR proceedings (2020-2026) was conducted. Data were extracted from primary studies applying GRACE to identify its impact on incremental cost effectiveness ratios (ICERs) and willingness-to-pay (WTP) thresholds. Current methodological guidelines from major HTA bodies were analyzed for GRACE alignment.
RESULTS: ICER (US) remains the primary formal adopter, integrating GRACE into its "Value Assessment Framework" for severe diseases. Five applications were identified: sickle cell disease (SCD), non-small cell lung cancer (NSCLC), Hepatitis C, and neurology. In SCD and NSCLC, GRACE increased WTP thresholds by ~50% and reduced ICERs by 7-13% respectively. In Hepatitis C, incorporating "insurance value" reduced ICERs by over 90%. In neurology, net monetary benefit increased by 11.6% through better valuing of disability prevention. Aggregate analysis of 69 drugs across 53 diseases demonstrated GRACE is budget-neutral, redistributing value from mild to severe conditions. GRACE principles increasingly appear in international HTA: NICE (UK) implemented 2026 threshold updates to £25,000-£35,000/QALY with "Severity Modifiers," while CADTH (Canada) and EU Member States shifted toward "Unmet Medical Need" weightings prioritizing severe health shortfalls.
CONCLUSIONS: GRACE systematically corrects undervaluation of treatments for severe conditions. Formal adoption by ICER and emergence of severity modifiers globally signal a significant shift from "flat" QALYs toward risk-adjusted models. While challenges exist regarding empirical estimation of risk-aversion parameters and measurement of untreated health baselines, the adoption of GRACE like method by major HTA bodies is a critical step toward more consistent and equitable healthcare resource allocation.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EE304
Topic
Economic Evaluation
Topic Subcategory
Thresholds & Opportunity Cost
Disease
No Additional Disease & Conditions/Specialized Treatment Areas