Reframing disease burden: validation of DALY-per-case as a per-diagnosis severity metric

Population-weighted metrics (incidence, mortality, disability-adjusted life years (DALYs), mortality to incidence ratio (MIR) can obscure per-case severity for less prevalent but high-impact conditions. This paper introduces DALY per case, total DALYs divided by incident cases, as a standardized estimate of healthy life-years lost per new diagnosis, integrating years of life lost (YLL) and years lived with disability (YLD). Validated using cancers and applied across diverse diseases, the metric enables prevalence-independent severity comparisons.

Using GBD 2021, we computed DALY per case across diseases (all ages, both sexes), validated on 34 cancers, and tested generalizability in five non-cancer conditions (type 2-diabetes, tuberculosis, HIV/AIDS, ischemic heart disease, Alzheimer's). We compared rankings with incidence, mortality, and total DALYs. A 2-Dimensional framework plotted total DALYs (population burden) vs. DALY-per-case (individual severity) with median-based quadrant thresholds. Uncertainty intervals (UIs) were propagated per GBD conventions; stability was assessed via relative UI width, band-crossing, and sensitivity analyses. Construct/convergent validity used correlations with 5-year survival Surveillance, Epidemiology, and End Results Program (SEER) and MIR; full and reduced regressions tested independence.

High-severity cancers included malignant bone tumours (27.6 DALYs/case), neuroblastoma (26.3), and brain/CNS (24.9), contrasting with population-dominant burdens such as lung (46.5 million DALYs; 20.4/case) and colorectal (24.4 million; 11.1/case). Relative uncertainty spanned 27% (breast) to 96% (Hodgkin lymphoma); rankings were largely preserved despite wide UIs in select sites. DALY-per-case correlated inversely with 5-year survival (r=-0.72, p < 0.001) and positively with MIR (r = 0.75, p < 0.001). In regression, MIR showed the strongest effect (β = 0.52, p = 0.06); survival lost significance when MIR was included, indicating shared but non-redundant variance.

DALY-per-case provides a disease-agnostic toolkit, including a 2Dimensional burden-severity framework and validation against existing indicators, to quantify per-diagnosis severity and inform policy across communicable and non-communicable diseases.