OBJECTIVES: Orphan drugs can address an unmet medical need but have relatively high prices and uncertainty regarding efficacy due to their small target populations. It is also argued that their value is not adequately captured in the QALY metric used in cost-utility analysis. These factors make it challenging for orphan drugs to meet national cost-effectiveness thresholds, influencing reimbursement decisions and patient access. This study aims to determine if a Multi-Criteria Decision Analysis (MCDA) framework can support orphan drug reimbursement decision-making in the Netherlands.

METHODS: A systematic literature review was conducted from January to April 2024 to identify potentially relevant (orphan) drug value determination criteria. Criteria for a draft MCDA framework were selected based on frequency and relevance claims in grey literature and according to the ISPOR MCDA guidelines. Interviews with 12 Dutch stakeholders (three pediatric clinicians, two hospital pharmacists, two patient representatives, two health economists, and three policymakers) refined the MCDA framework for orphan drugs. Preferences were elicited through prioritization, direct rating, and swing weighting methods and analyzed via ranked summed weighting and direct assignment techniques.

RESULTS: The literature review included 28 publications, describing 32 quantitative and 15 qualitative criteria. The draft MCDA framework incorporated 12 quantitative criteria (four with sub-criteria) and eight qualitative criteria. Interviews resulted in a final MCDA framework with five quantitative criteria: efficacy/effectiveness, disease severity/unmet (medical) needs, therapeutic impact/benefit, safety/tolerability, and quality of evidence, and four contextual criteria: opportunity costs and affordability, population priorities and access, system capacity and appropriate use of the intervention, and expert consensus/clinical practice guidelines. Moreover, dialogue reveals challenges in meeting nonoverlap, preference independence, and operational assumptions.

CONCLUSIONS: This research establishes a pioneering MCDA framework for evaluating first-in-class orphan drugs in the Netherlands to support healthcare decision-making. Even though all participants recognize its potential, there are still some hurdles to overcome.