In randomized clinical trials and observational studies, influenza vaccination has been shown to be effective in reducing influenza-related illness, hospitalizations, cardiovascular events, and mortality in select populations. However, the real-world effectiveness of influenza vaccination is limited by its uptake. Conducted during the 2023/2024 influenza season, the first NUDGE-FLU-CHRONIC trial demonstrated the effectiveness of behavioral nudging letters in increasing influenza vaccination rates among adults aged 18-64 years with chronic diseases in Denmark. This present study will once again investigate whether digital behavioral nudges delivered via the official, mandatory Danish electronic letter system can increase influenza vaccine uptake among adults aged 18-64 years with chronic diseases including whether the effectiveness of the previously successful strategies can be confirmed during a subsequent influenza season.

The study is a prospective, randomized, open-label implementation trial. The study population will consist of persons aged 18-64 years identified as eligible for free-of-charge influenza vaccination due to a chronic condition. Subjects will be identified through Danish nationwide health registries using codes from the International Classification of Diseases, 10th revision (ICD-10). Individuals will be randomized to 1 of 7 arms (1 usual care arm and 6 intervention arms) with each testing different nudging strategies employing various behavioural economic principles. The interventions will be delivered through the official, mandatory Danish electronic letter system. All subject data will be retrieved from the Danish nationwide registries with the exception of information on intervention allocation. Endpoints will be retrieved at prespecified dates using prespecified search algorithms.

Inclusion Criteria:

1. Age 18-64 years

2. Must be registered in the Danish nationwide registries as meeting at least one of the following eligibility criteria for free-of-charge influenza vaccination in the Danish public health system:

   1. Chronic lung disease
   2. Chronic cardiovascular disease other than hypertension
   3. Type 1 or type 2 diabetes mellitus
   4. Congenital or acquired immunodeficiency
   5. Impaired breathing due to muscular weakness
   6. Chronic renal or hepatic insufficiency
   7. Other chronic conditions with an increased risk of severe influenza as determined by the treating physician

3. Access to the official, mandatory Danish electronic mailbox system

Exclusion Criteria:

None

Data will be collected from Danish administrative health registries, which are subject to Danish legislation and can only be made available to a third party under certain conditions. Please contact the sponsor-investigator in case of any inquiries.