Do Orphan drugs deserve preferential treatment in HTAs and access?: The Netherlands re-thinks its approach

In 2022, the Netherlands introduced the Orphan Drug Access Protocol (ODAP) to address a familiar rare disease dilemma: how can patients receive timely access to promising treatments when the available evidence remains uncertain to support conventional reimbursement?

Four years later, the Dutch government is reconsidering whether orphan medicines should continue to benefit from a distinct access route. Its emerging position is that rarity alone should not justify preferential reimbursement, although a separate approach might still be needed for ultra-rare therapies [1]. Strictly speaking, this proposed policy redesign, expected to be incorporated into the future Dutch medicines system, the Toekomstbestendig Stelsel Geneesmiddelen (TSG) is not yet in force¹.

How has ODAP worked?

ODAP was developed for non-oncology orphan medicines whose evidence supported a positive assessment against the Dutch standard of established science and medical practice (stand van de wetenschap en praktijk)². Rather than granting unrestricted reimbursement, through ODAP, treatment was limited through predefined eligibility criteria and outcomes were assessed at the individual-patient level. Insurers paid for the treatment when patients achieved agreed outcomes, while evidence collected across the treated population was intended to support an eventual decision on definitive reimbursement^1,2. In this respect, ODAP aimed to align 3 objectives:

• Earlier access for patients with limited treatment options
• Evidence generation in Dutch clinical practice
• Financial risk-sharing through appropriate use and outcomes-based agreements

However, there is a practical evidence problem. Manufacturers consulted during the policy evaluation indicated that, where international registration studies provide insufficient evidence, collecting data from the smaller Dutch population is unlikely to generate enough evidence for a definitive reimbursement decision¹.

What would change?

Under the proposed direction, orphan medicines would no longer benefit from a separate access route simply because they carry orphan designation. The government's position is that manufacturers should, in principle, demonstrate the medicine's effectiveness before it is included in the basic health insurance package. Most orphan medicines can already be assessed through the regular reimbursement process and the government notes that many have successfully entered the Dutch package through this route¹.

This does not necessarily mean that ODAP will disappear in its entirety. Elements of the protocol may still be retained within the TSG, including¹:

• Agreements on appropriate patient selection and use
• Financial arrangements
• Individual outcome monitoring
• Pay for performance agreements

For manufacturers orphan status will therefore become a weaker market access argument. A Dutch access strategy will need to demonstrate that the evidence package is sufficiently robust for reimbursement or clearly explain why the remaining uncertainty cannot reasonably be resolved through the international clinical development programme.

An exception for ultra-orphan medicines?

The government accepts that the conventional approach may be unrealistic for ultra-orphan therapies particularly treatments intended for only a handful of patients. ZIN (Zorginstituut Nederland) has therefore proposed a separate route for ultra orphan medicines within the future TSG, a direction supported by the government. The precise definition evidentiary requirements and approach to cost effectiveness have not yet been established. Dutch policy documents note that the prevalence threshold of one patient per 50,000 people is sometimes used although no definitive Dutch threshold has been adopted¹. The emerging distinction is therefore not simply between common and rare diseases. It is between medicines for which evidence is difficult but still feasible to generate and those for which conventional evidence requirements may be structurally unattainable.

A more demanding but potentially clearer system

The proposed reform marks a move away from rarity-based preferential access towards evidence-based differentiation. For most orphan medicines manufacturers will remain responsible for demonstrating effectiveness before routine reimbursement. For ultra orphan, treatments the Netherlands may preserve a tailored pathway acknowledging that applying conventional standards too rigidly could make access practically impossible. The central challenge will be ensuring that “no preferential treatment for orphan drugs” does not become “no feasible route to access orphan drugs”. The credibility of the new approach will ultimately depend on whether the Netherlands can maintain rigorous evidence standards while recognising the genuine methodological limitations for evaluating value of treatment in ultra small patient populations.

Article by Demetria-Ilinca Panait

Sources

1. Dutch Ministry of Health, Welfare, and Sport (2026). Policy appraisal of the evaluation of conditional inclusion for orphan medicines, conditionals and exceptionals. Available at: https://open.overheid.nl/overheid/openbaarmakingen/api/v0/attachment/8b636b32-f1e8-475a-8e92-2d4272c62373[Accessed 6 August 2026]
2. Zorginstituut Nederland (2023). Q&A on conditional inclusion, DAP and ODAP. Available at: https://www.zorginstituutnederland.nl/site/binaries/site-content/collections/documents/2023/09/29/qa-voorwaardelijke-toelating-weesgeneesmiddelen-conditionals-en-exceptionals/Veelgestelde+vragen+VT+weesgeneesmiddelen%2C+conditionals+en+exceptionals.pdf [Accessed 6 August 2026)

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