Orphan drug assessment: is a special approach required?

The journal PharmacoEconomics (2025) published an article analyzing the limitations of current health technology assessment (HTA) procedures for orphan drugs and proposing ways to adapt the system.

The authors emphasize: evidence on rare diseases is not just rare—it requires a special approach to interpretation and use in decision-making.

Main problems highlighted in the study:

• Lack of data on the natural history of the disease—there are no cohort observations, making it difficult to predict outcomes without therapy and calculate effectiveness and utility indicators (e.g., QALYs).

• Underrepresentation in classifications, including the ICD — the lack of codes in the International Classification of Diseases complicates patient identification, registry creation, and budget impact analysis.

• Small sample sizes in clinical trials — most often less than 100 patients, which limits the statistical reliability of results and increases uncertainty in cost-effectiveness models.

• Lack of randomized controlled trials — for ethical reasons; external control groups and indirect comparisons (MAIC, STC) are used, which are not always accepted by HTA agencies.

• Lack of validated endpoints—scales are often borrowed from other diseases and do not take into account patient-specific symptoms and the impact on families.

Proposed solutions:

• Expand the scope of value assessment—take into account direct medical costs, as well as non-medical and indirect costs, the impact on families, and spillover effects.

• Implementation of managed access agreements — temporary inclusion of a drug for reimbursement with subsequent data collection (examples: Cancer Drugs Fund, Innovative Medicines Fund, UK).

• Application of multicriteria decision analysis (MCDA) — multicriteria analysis that takes into account clinical efficacy, disease severity, rarity, lack of alternatives, impact on the family, and principles of equity and solidarity. Elements of MCDA are already being applied in France, Canada, and Scotland.

• Harmonization of registration and health technology assessment requirements — implementation of parallel scientific consultation between registration agencies and HTA agencies.

Source  (https://link.springer.com/article/10.1007/s40273-025-01538-4)

Download document: HTA Evidence in Rare Diseases: Just Rare or Also Special? (https://drive.google.com/file/d/1-l0i5YECQIItQX4BeXzwje0mqVSm62cW/view?usp=sharing)