APPLYING THE GENERALIZED RISK-ADJUSTED COST-EFFECTIVENESS FRAMEWORK TO DERIVE WILLINGNESS-TO-PAY THRESHOLDS FOR ER+/HER2-/ESR1+ METASTATIC BREAST CANCER

Author(s)

William Vincent Padula, PhD1, Benjamin Cohen, MPH, PhD2, Paul Garrett Steel, MHS2, Santiago Moreno, PhD3, Federico Felizzi, BSc, MS, PhD3.
1University of Southern California, Rancho Palos Verdes, CA, USA, 2Stage Analytics, Suwanee, GA, USA, 3Menarini, Florence, Italy.
OBJECTIVES: Traditional cost-effectiveness analysis (CEA) evaluates health technologies against a fixed willingness-to-pay (WTP) threshold (commonly $100,000-$150,000 per quality-adjusted life year [QALY]), assuming constant returns to health and risk-neutral decision-making. These assumptions may underestimate value in severe conditions such as ER+/HER2−/ESR1+ metastatic breast cancer (mBC). This study applies the Generalized Risk-Adjusted Cost-Effectiveness (GRACE) framework to derive disease-specific WTP thresholds.
METHODS: Following Mulligan et al., KGRACE = K (conventional threshold) × ωH (elasticity of utility with respect to health) × R (disease severity ratio) × D (disability ratio), with parameters informed by literature, clinical input, and patient-level data (ωH = 0.45; R = 3.1; D = 1.9). Published EQ-5D utilities for ER+/HER2−/ESR1+ mBC (progression-free: 0.837; progressed disease: 0.443) were mapped using Basu-Lakdawalla EP2 equations to generate risk- and severity-adjusted QALYs (GRA/GRASA) and corresponding WTP adjustment factors. Both GRASA (risk and severity-adjusted) and GRA (risk-adjusted only) specifications were evaluated.
RESULTS: Using the Mulligan et al. formula, WTP thresholds ranged from $265,050-$397,575 (based on $100,000 and $150,000/QALY). Under the GRASA specification, utilities mapped to 0.778 (progression-free) and 0.439 (progressed), yielding an adjustment factor (λEP2,GRASA-QALY) of approximately 1.92. Corresponding GRACE-adjusted WTP thresholds were ~$192,000 and ~$288,000. Under the GRA specification, utilities mapped to 0.829 and 0.311, yielding an adjustment factor (λEP2,GRA-QALY) of 1.76 with corresponding thresholds of ~$177,000 and ~$265,000. Across approaches, GRACE produced increased WTP thresholds, primarily driven by disease severity.
CONCLUSIONS: The GRACE framework provides an empirically grounded approach to translate risk preferences and EQ-5D data into adjusted WTP thresholds without requiring bespoke inputs. In ER+/HER2−/ESR1+ mBC, GRACE yields higher WTP thresholds than conventional CEA, reflecting high disease severity. These findings support GRACE as a complementary value assessment approach for severe oncology indications.

Conference/Value in Health Info

2026-11, ISPOR Europe 2026, Vienna, Austria

Value in Health, Volume 29, Issue 12S

Code

CO128

Topic

Clinical Outcomes

Disease

Oncology

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