Making trade-offs explicit: development and pilot of a Belgian MCDA framework for orphan drug appraisal

Orphan drug reimbursement remains a contested area in health technology assessment (HTA), as decision makers must balance limited evidence, high unmet need, patient-relevant value, and affordability. Multi-criteria decision analysis (MCDA) has been proposed to make such trade-offs more explicit and transparent, yet empirical applications in European national HTA settings remain scarce.

We developed and piloted an MCDA framework for orphan drug reimbursement in Belgium. Candidate criteria were identified through a systematic literature review. A multidisciplinary expert panel (comprising representatives from the national reimbursement agency, sickness funds, patient organizations, pharmaceutical companies, clinicians, and bioethicists) participated in four focus group discussions to select and define criteria. Criterion weights were elicited through a three-round Delphi process. The framework was piloted on four orphan drugs previously appraised in Belgium: ponatinib, pirfenidone, onasemnogene abeparvovec, and metreleptin.

Seven quantitative and three qualitative contextual criteria were selected. Unmet medical need received the highest weight, followed by comparative effectiveness and impact on patient-reported outcomes. Onasemnogene abeparvovec achieved the highest overall MCDA score (0.77), followed by metreleptin (0.65), pirfenidone (0.47), and ponatinib (0.39). The pilot also generated policy-relevant insights on criterion design, handling residual uncertainty, separating value assessment from reimbursement feasibility (through cost criteria), and using scores to support-rather than replace-deliberation.

This study presents the first MCDA framework for orphan drug reimbursement in Belgium and illustrates how criterion weights and scores can structure committee deliberation, complemented by contextual appraisal, to support more transparent, consistent, and accountable decision making.