Incremental cost per quality-adjusted life year gained? The need for alternative methods to evaluate medical interventions for ultra-rare disorders

J Comp Eff Res. 2014 Jul;3(4):399-422. doi: 10.2217/cer.14.34.


Drugs for ultra-rare disorders (URDs) rank prominently among the most expensive medicines on a cost-per-patient basis. Many of them do not meet conventional standards for cost-effectiveness. In light of the high fixed cost of R&D, this challenge is inversely related to the prevalence of URDs. The present paper sets out to explain the rationale underlying a recent expert consensus on these issues, recommending a more rigorous assessment of the clinical effectiveness of URDs, applying established standards of evidence-based medicine. This may include conditional approval and reimbursement policies, which should be combined with a firm expectation of proof of a minimum significant clinical benefit within a reasonable time. In contrast, current health economic evaluation paradigms fail to adequately reflect normative and empirical concerns (i.e., morally defensible 'social preferences') regarding healthcare resource allocation. Hence there is a strong need for alternative economic evaluation models for URDs.

Keywords: consensus statement; cost–effectiveness; economic evaluation; fairness; health technology assessment; medical ethics; medical need; orphan medicines; quality-adjusted life year; social preferences.

MeSH terms

  • Consensus
  • Cost-Benefit Analysis*
  • Evidence-Based Medicine
  • Health Care Costs
  • Humans
  • Models, Economic
  • Outcome Assessment, Health Care / methods*
  • Quality-Adjusted Life Years*
  • Rare Diseases / economics
  • Rare Diseases / therapy*
  • Technology Assessment, Biomedical