In 2024, the Netherlands introduced what is now widely regarded as the most scientifically rigorous health-economic evaluation guideline in Europe. For companies preparing submissions in 2025, the key issue is no longer what the guideline says, but how to apply it correctly to strengthen a reimbursement case under this modernised Dutch HTA framework.
While many European HTA systems remain anchored in narrow payer perspectives, limited probabilistic methods, and inconsistent treatment of uncertainty, Zorginstituut Nederland (ZIN) has moved decisively toward a decision-science-based approach. The new standard integrates welfare economics, full societal modelling, robust uncertainty analysis, and mandatory value of information (VOI) techniques into the reference case.
This shift raises the bar for industry, but it also creates a strategic opportunity:
Submissions that use these updated methods correctly can demonstrate significantly greater credibility, scientific rigor, and economic value.
This article explains how companies should prepare ZIN-compliant submissions in 2025, drawing on the official guideline and the latest methodological clarifications.
1. Begin With the Full Societal Perspective Not a Minimal Productivity Add-On
ZIN now requires the most comprehensive operationalisation of the societal perspective used by any major HTA body. However, many submissions still misinterpret this requirement, adding only productivity losses and informal care hours. This is no longer sufficient — and is a common reason for ZIN requests for clarification.
A fully compliant societal perspective in 2025 must include:
✔ Direct healthcare costs
Using the updated costing manual, including:
– diagnostics (laboratories, imaging, microbiology, pathology)
– mental healthcare
– drug administration
– specialist nursing
– primary and community care
✔ Direct non-health costs
Crucial for interventions affecting broader social systems:
– education
– justice
– social care and welfare services
✔ Productivity losses using the friction-cost method
Not the human-capital method.
This requires updated 2024/2025 labour-market parameters, as specified in the revised costing manual.
✔ Informal care and caregiver quality-of-life impacts
ZIN expects caregiver disutility to be modelled using EQ-5D-5L or validated mapping methods.
This is now a core requirement, not a sensitivity option.
✔ Unrelated future medical costs in extended survival
Mandatory in the base case — no longer allowed as scenario analysis only.
A submission that omits any component without clear scientific justification will lose credibility.
The standard is demanding, but when implemented correctly, a societal-perspective model becomes a powerful value-demonstration tool.
2. Use Mandatory Probabilistic Analysis Correctly PSA Is Now Core Evidence
Historically, many dossiers treated probabilistic sensitivity analysis (PSA) as an optional appendix. ZIN has now embedded PSA directly into the reference case, alongside VOI.
A correct 2025 PSA must:
- Assign probability distributions to all uncertain parameters.
- Apply joint distributions wherever correlation exists (e.g., utility estimates, relative risks, cost clusters).
- Present probabilistic ICERs, not only deterministic estimates.
- Include cost-effectiveness acceptability curves (CEACs) using Dutch-specific willingness-to-pay thresholds.
- Integrate EVPI and EVPPI analyses to quantify decision uncertainty.
PSA must appear in the main body of the report, not buried in annexes.
For ZIN, PSA is now a decision tool — not an afterthought.
3. Integrate VOI as a Decision Framework Not a Decorative Appendix
One of the most significant methodological innovations is ZIN’s explicit requirement to include value of information (VOI) in the reference case.
This represents a profound shift in HTA practice because VOI:
• Reframes reimbursement as a decision under uncertainty
It quantifies whether the residual uncertainty is acceptable or whether further research is warranted.
• Supports conditional reimbursement
High EVPI combined with large expected population benefit can justify coverage with evidence development.
• Allows industry to proactively propose evidence-generation plans
Instead of waiting for ZIN to mandate additional studies.
A strong VOI section should include:
- EVPI for total decision uncertainty
- EVPPI for key cost-effectiveness drivers
- Interpretation of whether uncertainty should be reduced through further study
- A proposed Dutch evidence-generation plan (registry, pragmatic trial, RWE, cluster study)
- Budget implications of delaying or accelerating adoption
Companies that use VOI effectively can influence ZIN’s research requirements and shape a more favourable pathway to reimbursement.
4. Apply Modern Statistical Standards for Trial-Based Economic Evaluations
ZIN has aligned trial-based evaluations (TBE) with modern statistical practice. Submissions must now demonstrate:
- Adjustment for clustered trial designs
- Baseline covariate adjustment
- Multiple imputation for missing data
- Bootstrapping to generate cost-effect pairs
- Coherence between trial-based and model-based results
Errors in TBE analyses are among the most common reasons ZIN requests clarification.
Getting this section right significantly strengthens methodological credibility.
5. Handle Expert Elicitation With Rigour ZIN Has Tightened the Rules
Expert elicitation is sometimes required for early models or sparse data.
However, the new guidelines impose strict methodological standards:
- Clear separation between qualitative interviews and quantitative elicitation
- Transparent declaration of all conflicts of interest
- Use of formal mathematical aggregation methods (e.g., linear pooling)
- Justification of the elicitation framework (e.g., Sheffield Elicitation Framework)
Poor elicitation is a known weakness in many dossiers; high-quality elicitation can greatly improve model integrity and reduce uncertainty.
6. Use the Expanded Dutch Costing Manual Correctly and Comprehensively
The 2024/2025 costing update is far broader than before, covering:
- diagnostics across all laboratory domains
- imaging
- microbiology
- pathology
- mental health services
- drug preparation and administration
- primary care and community services
- justice, welfare, and education services
For interventions outside narrow clinical pathways — such as AMR diagnostics, behavioural health interventions, paediatric programmes, or chronic disability — correct use of these cost categories is essential.
Failure to apply updated unit costs is one of the most common causes of ZIN methodological critique.
7. Anticipate Future Changes: WTP Recalibration and EQ-HWB Pilots
Two major methodological shifts are already underway and may affect submissions after 2025.
✔ 1. Willingness-to-pay (WTP) threshold recalibration
The traditional €20,000 / €50,000 / €80,000 bands are under review.
ZIN is moving toward a continuous threshold function tied to disease burden — similar to the severity approach used in Norway.
✔ 2. Broader outcome measures: EQ-HWB and capability tools
For long-term, non-curative, social, or mental-health interventions, ZIN is piloting:
- EQ-HWB (well-being measure)
- ICECAP-A / ICECAP-O (capability measures)
Forward-looking submissions can gain resilience by incorporating:
- scenario analyses using alternative WTP functions
- sensitivity analyses using capability-based outcomes
This prepares the dossier for policy evolution without requiring full redevelopment.
8. What a High-Quality 2025 ZIN Submission Looks Like
A rigorous, modern, ZIN-aligned submission should demonstrate:
🔹 A complete societal-perspective model, including spillovers
🔹 Full PSA integrated into the reference case
🔹 Mandatory VOI analysis (EVPI/EVPPI) with clear interpretation
🔹 Correct friction-cost method productivity modelling
🔹 Inclusion of unrelated future medical costs
🔹 Updated Dutch cost data across all relevant sectors
🔹 Evidence-based modelling of caregiver QoL
🔹 Statistically robust TBE analysis
🔹 A proposed Dutch RWE or registry design informed by VOI
This is the level of scientific and methodological quality ZIN now expects.
It is more demanding than any other European HTA body — but for companies that apply the standard correctly, it creates a powerful platform for demonstrating true value, reducing uncertainty, and securing a favourable reimbursement decision.
Reference
Official Government & HTA Sources
Zorginstituut Nederland (2024). Guideline for Economic Evaluations in Healthcare.
The official Dutch national guideline outlining methodological standards for cost-effectiveness, societal perspective, uncertainty analysis, VOI, and modelling requirements. This is the authoritative source for all ZIN submissions from 2024 onward.
Available at: https://english.zorginstituutnederland.nl/documents/2024/01/16/guideline-for-economic-evaluations-in-healthcare
Zorginstituut Nederland (2024). Working Methods and Procedures.
Explains ZIN’s assessment processes, evidence requirements, procedural rules, and the decision-making framework used in Dutch HTA evaluations.
Available at: https://english.zorginstituutnederland.nl/about-us/working-methods-and-procedures
Zorginstituut Nederland (2024). Publications and Cost Price Studies.
Repository of annual costing manual updates, diagnostic cost modules, methodological reports, and cost-price studies that must be used when valuing resources in Dutch submissions.
Available at: https://english.zorginstituutnederland.nl/publications
Statistics Netherlands (CBS). Labour Market and Productivity Data.
Provides official data on employment, wages, vacancy duration, and labour-market parameters. This is the required source for applying the friction-cost method in ZIN-compliant productivity analysis.
Available at: https://www.cbs.nl/en-gb
Peer-Reviewed Academic Sources — VOI, Decision Science & HTA Methods
Fenwick, E., Steuten, L. & Claxton, K. (2020). ‘Value of Information Analysis: Report 1’. Value in Health.
The first ISPOR Task Force report on VOI methodology. Defines key concepts (EVPI, EVPPI, EVSI), recommended reporting standards, and best practices. Forms the scientific backbone of ZIN’s VOI requirements.
Available at:
https://www.valueinhealthjournal.com/article/S1098-3015(20)30027-9/fulltext
Jalal, H. et al. (2020). ‘Value of Information: Analytical Methods’. Value in Health.
The second ISPOR Task Force report covering the analytical models, computational approaches, and mathematical foundations of VOI analysis — required for implementing VOI in Dutch submissions.
PubMed link: https://pubmed.ncbi.nlm.nih.gov/32197720/
Geuzinge, H.A. et al. (2025). ‘The New Dutch Guideline for Economic Evaluations’. Value in Health.
Provides academic context, rationale, and implications for the 2024 Dutch guideline revision, including societal perspective expansion, discounting changes, and VOI adoption.
Available at:
https://www.sciencedirect.com/science/article/pii/S1098301525001160
Tuffaha, H.W., El Saifi, N. & Scuffham, P.A. (2021). ‘Value of Information Analysis: Are We There Yet?’. PharmacoEconomics.
A comprehensive review of VOI theory and real-world application. Useful for designing VOI components in HTA submissions and interpreting ZIN’s requirements.
Available at:
https://link.springer.com/article/10.1007/s41669-020-00227-6
Additional Relevant Academic Sources — Outcomes, Discounting, Preference Measures
Attema, A.E., Brouwer, W.B.F. & Van Exel, J. (2018). ‘Discounting in Economic Evaluation’. Journal of Health Economics.
Seminal analysis supporting the shift toward a 3% cost discount rate and methodological coherence across long-term models. Influential in shaping modern Dutch discounting rules.
Available at:
https://www.sciencedirect.com/science/article/pii/S0167629618303151
Brazier, J. et al. (2022). ‘Developing the EQ-HWB Measure’. Health and Quality of Life Outcomes.
Foundational paper on the EQ-HWB (well-being measure), now under consideration by ZIN for long-term and social-care-related interventions. Important for anticipating future Dutch methodological updates.
Available at:
https://hqlo.biomedcentral.com/articles/10.1186/s12955-022-02001-7