Does conventional cost-effectiveness analysis disadvantage treatments for severe disease? Evidence from U.S. value...

To assess how frequently QALY-based and LY-based incremental health benefits meaningfully differ and whether those differences affect cost-effectiveness conclusions; how these differences vary across disease categories and what disease severity composition underlies this variation; and whether the QALY-LY difference is associated with baseline disease severity.

We analyzed 167 treatment-comparator assessment pairs from 71 Institute for Clinical and Economic Review reports (2017-2025), spanning 65 conditions across eight disease categories. We compared incremental QALYs and LYs, assessed cost-effectiveness concordance at $100,000 and $150,000 thresholds, and examined cross-category variation. In a restricted sample of 82 pairs, we assessed associations between severity measures and the QALY-LY difference using linear regression and Spearman rank correlation.

QALYs showed greater incremental gains than LYs in 59% of assessments; LYs were greater in 22%. Cost-effectiveness conclusions were highly concordant (92.2% at $100,000; 87.4% at $150,000), though QALYs classified 20-32% more interventions as cost-effective. The QALY-LY difference varied significantly across disease categories (p<0.001), reflecting differences in disease burden composition. Neither LY lost nor evLY lost was meaningfully associated with the QALY-LY difference. The only significant association emerged for baseline health-related quality of life under standard care, where greater impairment was associated with larger incremental gains with QALYs relative to LYs. Both metrics scaled proportionally with disease severity.

QALY-based cost-effectiveness does not systematically disadvantage treatments for more severe disease. Replacing QALYs with LYs would omit therapeutic value most relevant to high-morbidity populations, potentially working against the interests of the patient populations this policy debate seeks to protect.