Pharmacoeconomics. 2026 May 5. doi: 10.1007/s40273-026-01616-1. Online ahead of print.
ABSTRACT
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, progressive condition associated with high per-patient treatment costs and substantial clinical burden. Interpreting cost-effectiveness evidence for rare diseases remains challenging when uniform thresholds are applied across conditions that differ markedly in prevalence and scale of healthcare production.
OBJECTIVE: The aim of this study was to estimate a prevalence-adjusted effective cost-effectiveness threshold for PAH and illustrate how disease prevalence and production scale influence the interpretation of cost-effectiveness evidence under a fixed health care budget.
METHODS: We applied a previously developed prevalence-adjusted cost-effectiveness threshold framework, referred to as a generalized dynamic prevalence (GeDP) approach, to PAH using nationally representative disease prevalence data from the Medical Expenditure Panel Survey. A flexible statistical transformation was used to accommodate the highly right skewed distribution of disease prevalence and to estimate the relationship between prevalence and effective thresholds. The analysis was anchored to an empirically estimated US health opportunity cost benchmark and applied to PAH, with comparisons to selected common and rare diseases. Illustrative scenarios examined how effective thresholds evolve under changes in disease prevalence over time.
RESULTS: Effective cost-effectiveness thresholds increased as disease prevalence declined, reflecting production-side scale effects rather than differences in societal preferences. For PAH (prevalence ≈ 0.013%), the prevalence-adjusted effective threshold was estimated at US$582,270 per QALY (95% CI 581,319-583,163), representing more than a five-fold increase relative to the reference opportunity-cost benchmark of US$104,000 per QALY applied to highly prevalent conditions. Dynamic scenarios showed that effective cost-effectiveness thresholds decline as prevalence changes over time, with larger adjustments observed for initially rare conditions.
CONCLUSION: Applying a uniform cost-effectiveness threshold across diseases implicitly assumes homogeneous production conditions and opportunity costs. Prevalence-adjusted effective thresholds derived under the GeDP framework provide a quantitative, descriptive approach for contextualizing cost-effectiveness evidence for rare diseases such as PAH without redefining societal willingness to pay or prescribing decision rules. This approach can complement existing pharmacoeconomic evaluations by improving transparency around the role of prevalence and scale in shaping opportunity costs.
PMID:42084829 | DOI:10.1007/s40273-026-01616-1
