Updated health-economic evidence, drawing on data from more than 85 million individuals, confirms that switching from standard-dose to high-dose influenza vaccination would prevent thousands of hospitalisations each year, at a cost well within accepted thresholds.
Influenza places a substantial burden on healthcare systems every winter. Older adults face disproportionate risk: age-related changes in immune function, combined with a higher prevalence of underlying conditions, make them more vulnerable to severe disease and hospitalisation. Vaccination programmes are the primary tool for reducing this burden, but not all vaccines offer the same level of protection.
High-dose inactivated influenza vaccination (HD-IIV), registered in the Netherlands for adults aged 60 and over, delivers four times the antigen content of standard-dose formulations. It has consistently demonstrated superior protection against influenza-related illness and hospitalisation, in both randomised clinical trials (RCTs) and real-world evidence (RWE). Despite this, HD-IIV has not yet been incorporated into the Dutch National Immunisation Programme (NIP).
In December 2024, the Dutch Health Council (Gezondheidsraad) concluded that HD-IIV or adjuvanted influenza vaccine can be included in the NIP for adults aged 60 and over, provided the cost-effectiveness case is established. An earlier analysis by Van der Pol et al. in 2024 demonstrated that HD-IIV is cost-effective under the evidence available at the time. Since then, a substantial body of new clinical evidence has emerged, warranting an updated economic assessment.
Our updated and recently published analysis uses the same validated decision-tree model as the 2024 study(1), now incorporating the latest effectiveness data from two major sources: a pooled meta-analysis of RCT and real-world data covering more than 85 million individuals across 15 influenza seasons, and the FLUNITY-HD trial, an individually randomised pooled analysis of 466,320 adults in Denmark and Spain, conducted across the 2022–2025 seasons.
The updated relative vaccine effectiveness (rVE) of HD-IIV versus standard-dose vaccination is 24% against influenza-like illness and 7% against cardiorespiratory hospitalisations under RCT evidence alone; 15% and 8% respectively when real-world evidence is incorporated. These figures are more conservative than the 2024 analysis, partly because high co-vaccination rates with COVID-19 and pneumococcal vaccines in the FLUNITY-HD trial population reduced the overall risk of cardiorespiratory disease in both arms. Despite this, the incremental cost-effectiveness ratios (ICERs) remain well below the Dutch willingness-to-pay thresholds of €20,000 and €50,000 per QALY gained.
Probabilistic sensitivity analysis, across 1,000 simulations, confirms that HD-IIV is cost-effective in more than 99% of scenarios at the €20,000/QALY threshold, and 100% at €50,000/QALY. The conclusion holds across all scenario and sensitivity analyses.
The analysis is explicit about the remaining barriers. The primary barrier to implementation is the upfront cost: HD-IIV is priced at €32 per dose versus €8 for standard-dose vaccination. Even at list price, the analysis shows this investment would be largely returned through reduced GP consultations and prevented hospitalisations. A negotiated procurement price could shift the balance further, potentially achieving net savings within national healthcare budgets.
One evidence gap remains: no head-to-head data yet compare HD-IIV with adjuvanted influenza vaccine (aIV), the other enhanced formulation under consideration by the Dutch Health Council. A trial currently under way may eventually enable an indirect comparison. The model used in the recent publication does not capture all downstream consequences, including long-term care after hospitalisation and nursing home mortality. Incorporating these parameters would likely strengthen the cost-effectiveness case further.
Taken together, this updated analysis directly supports the Dutch Health Council's 2024 recommendation: HD-IIV is a valid option for inclusion in the NIP for adults aged 60 and over.
This research was conducted by Simon van der Pol, Sajad Emamipour, Anita van Oudheusden, Bas Slierendregt, Gerald Moncayo and Cornelis Boersma, Published in Vaccine: X , Volume 31, 2026 and supported by Sanofi Netherlands. Full conflict-of-interest disclosure is available in the published article.
Reference:
1. van der Pol S, Zeevat F, Postma MJ, Boersma C. Cost-effectiveness of high-dose influenza vaccination in the Netherlands: incorporating the impact on both respiratory and cardiovascular hospitalizations. Vaccine 2024;42:3429–36. https://doi.org/10.1016/j.vaccine.2024.04.040.