The reimbursement of orphan medicinal products (OMPs) for rare diseases remains one of the most complex challenges in European healthcare policy. These therapies frequently launch with limited clinical evidence, small target populations and high per-patient costs—a triad that stretches both ethical and budgetary boundaries.
The Orphan Drug Access Protocol (ODAP) in the Netherlands offers a promising innovation. Designed by Zorginstituut Nederland (ZIN) in collaboration with the Dutch Ministry of Health (VWS), ODAP is a hybrid managed entry scheme that blends individual-level outcome-based reimbursement (OBA) with population-level coverage with evidence development (CED), marking a new frontier in personalised yet sustainable drug access.
| Ministry of Health, Welfare and Sport | Government.nl The ambition of the Ministry of Health, Welfare and Sport is to keep everyone healthy as long as possible and to restore the sick to health as quickly as possible.www.government.nl |
ODAP is a five-year pilot scheme (2023–2028), targeting non-oncology orphan drugs with:
- EMA marketing authorisation (or expected within 9 months)
- Use limited to inpatient hospital settings
- < €10M annual budget impact
- High uncertainty in clinical effectiveness
- Addressing unmet clinical need
ODAP proceeds in three scientific-phased stages:
🔹 Phase 1: Individual Assessment of Effectiveness
A National Indication Committee, including clinical experts, rare disease specialists and pharmacologists, assesses each patient’s eligibility and tracks drug response using predefined clinical outcome measures, which may include functional scores, biomarker levels or patient-reported outcomes (PROMs).
🔹 Phase 2: Conditional Reimbursement per Patient
If outcomes are met, health insurers reimburse the drug for that patient. Non-responders are withdrawn—ensuring resource allocation is restricted to those who benefit.
🔹 Phase 3: Real-World Evidence & Population-Level Analysis
Data are collected via national or international disease registries, enabling:
- Subgroup analysis
- Longitudinal outcomes tracking
- Cost-effectiveness evaluation (e.g. ICER, QALY-based modelling)
- Potential biomarker development to predict response
Reimbursement agreements are confidential and dynamic, adjusted at each phase based on the strength of evidence.
Three therapies are already under evaluation:
- Oxlumo® (lumasiran) – Alnylam Pharmaceuticals
▸ For Primary Hyperoxaluria Type 1
▸ RNAi therapeutic targeting glycolate oxidase
▸ EMA orphan designation: ✔️
▸ Reference: Garrelfs et al., New England Journal of Medicine, 2021 - Enjaymo® (sutimlimab) – Recordati Rare Diseases
▸ For Cold Agglutinin Disease (CAD)
▸ Humanised monoclonal antibody targeting classical complement pathway (C1s)
▸ Reference: Röth et al., Blood, 2021 - Qalsody® (tofersen) – Biogen
▸ For SOD1-mediated ALS
▸ Antisense oligonucleotide (ASO) targeting SOD1 mRNA
▸ Reference: Miller et al., NEJM, 2022
A recent Lancet Public Health commentary (2024) highlights that ODAP improves transparency in decision-making, fosters clinician collaboration and promotes scientific rigour in drug withdrawal when ineffective. The author noted that:
“ODAP stimulates selective access based on stringent scientific criteria, enhancing rational use of high-cost therapies and enabling the construction of disease-specific evidence bases.”
The implementation of ODAP involves coordination between several Dutch and international stakeholders:
| Organisation | Role |
| Zorginstituut Nederland (ZIN) | HTA body coordinating ODAP evaluation, RWE frameworks, and population-level decisions |
| Ministry of Health, Welfare and Sport (VWS) | Policy lead and funding oversight |
| Dutch Health Insurers (ZN) | Payors negotiating confidential reimbursement contracts |
| National Indication Committees | Multidisciplinary panels guiding patient-level inclusion |
| International Registries & EJP RD Network | Data sources and harmonisation for cross-border analysis |
| Academic Centres (e.g., UMC Utrecht, Radboudumc) | Centres of excellence involved in protocol design and evaluation |
The ODAP framework is notable for its alignment with broader European trends in personalised, outcomes-based healthcare:
🔹 In Germany, it offers a structured post-AMNOG alternative for orphan drugs that fail early benefit assessments.
🔹 In France, it complements early access systems like Accès Précoce and the Forfait Innovation with better long-term data integration.
🔹 In Belgium or Austria, ODAP could be a launchpad for collaborative registries and international CED schemes under EUnetHTA 21 principles.
🔹 It could also support joint clinical assessments (JCAs) for ultra-rare diseases under the EU HTA Regulation (EU/2021/2282), which enters force in 2025–2028.
In a space often dominated by high-cost drugs, small datasets and uncertain outcomes, ODAP introduces a compelling scientific and policy experiment. It aligns clinical practice with HTA evidence, builds national and international rare disease intelligence, reduces financial risk to payers and enhances scientific understanding of ultra-rare diseases through longitudinal RWE.
The pilot status means refinements are expected, but if successful, ODAP could become a leading European model for rational, equitable, and science-based orphan drug access.