Nationwide Utilization of Danish Government Electronic Letter System for Confirming the Effectiveness of Behavioral Nudges in Increasing InFLUenza Vaccine Uptake Among Adults With Chronic Disease

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.

Study Overview

• Status: Completed
• Conditions: Influenza; Behavior and Behavior Mechanisms
• Intervention / Treatment: Behavioral: Behavioral Economic Principles

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 308978
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Hellerup, Capital Region, Denmark, 2900
      • Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Letter; This group will receive a standard letter on the benefits of influenza vaccination without behavioral economic enhancement	Behavioral: Behavioral Economic Principles; The control arm will receive no letter to reflect the background vaccination uptake. Intervention arms will test the effects of different letters developed using behavioral economic principles.
No Intervention: Usual Care; No letter
Experimental: Repeated Letter; The standard letter sent out two times instead of once	Behavioral: Behavioral Economic Principles; The control arm will receive no letter to reflect the background vaccination uptake. Intervention arms will test the effects of different letters developed using behavioral economic principles.
Experimental: Cardiovascular Gain-Framing Letter; Text added to the standard letter highlighting potential cardiovascular benefits of influenza vaccination	Behavioral: Behavioral Economic Principles; The control arm will receive no letter to reflect the background vaccination uptake. Intervention arms will test the effects of different letters developed using behavioral economic principles.
Experimental: Respiratory Gain-Framing Letter; Text added to the standard letter highlighting potential respiratory disease-related benefits of influenza vaccination	Behavioral: Behavioral Economic Principles; The control arm will receive no letter to reflect the background vaccination uptake. Intervention arms will test the effects of different letters developed using behavioral economic principles.
Experimental: Implementation Intention Prompt Letter; Implementation intention prompt added to the standard letter	Behavioral: Behavioral Economic Principles; The control arm will receive no letter to reflect the background vaccination uptake. Intervention arms will test the effects of different letters developed using behavioral economic principles.
Experimental: Repeated Cardiovascular Gain-Framing Letter; The cardiovascular gain-framing letter sent out two times instead of once	Behavioral: Behavioral Economic Principles; The control arm will receive no letter to reflect the background vaccination uptake. Intervention arms will test the effects of different letters developed using behavioral economic principles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants who received an influenza vaccine	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time from intervention delivery to influenza vaccination	Up to 3 months

Other Outcome Measures

Outcome Measure	Time Frame
Number of participants with laboratory-confirmed influenza	Up to 8 months
Number of participants with any hospitalization	Up to 8 months
All-cause mortality	Up to 8 months
Composite of incident heart failure, heart failure hospitalization, or cardiovascular death	Up to 8 months
Composite of myocardial infarction, stroke, or cardiovascular death	Up to 8 months
Composite of myocardial infarction, coronary revascularization, stroke, or cardiovascular death	Up to 8 months
Number of participants with incident heart failure or heart failure hospitalization	Up to 8 months
Cardiovascular death	Up to 8 months
Number of participants with myocardial infarction	Up to 8 months
Number of participants with stroke	Up to 8 months
Number of contacts to general practitioner (excluding vaccination visit)	Up to 8 months
Number of participants with laboratory-confirmed COVID-19	Up to 8 months
Number of participants who received a COVID-19 vaccine	Up to 3 months
Number of participants with a hospitalization for influenza or pneumonia	Up to 8 months
Number of participants with a hospitalization for any respiratory disease	Up to 8 months
Number of participants with a hospitalization for any cardio-respiratory disease	Up to 8 months
Number of participants with a hospitalization for any cardiovascular disease	Up to 8 months
Total number of hospitalizations (first and recurrent)	Up to 8 months
Total number of heart failure events (incident heart failure and first and recurrent heart failure hospitalizations)	Up to 8 months
Number of participants with incident atrial fibrillation or atrial fibrillation hospitalization	Up to 8 months
Number of participants with a hospitalization for COVID-19	Up to 8 months
Number of participants who filled a prescription for any guideline-directed medical therapy for heart failure	Up to 8 months
Total number of filled prescriptions for guideline-directed medical therapy for heart failure	Up to 8 months
Number of participants who filled a prescription for a sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist	Up to 8 months
Number of participants with coronary revascularization	Up to 3 months

Collaborators and Investigators

• Sponsor: Tor Biering-Sørensen
• Investigators: Principal Investigator: Tor Biering-Sørensen, MD, MSc, MPH, PhD, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Actual): January 1, 2025
• Study Completion (Actual): May 31, 2025

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: September 13, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Influenza; Vaccination; Registry; Randomized Trial; Behavioral Science; Nudging
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Behavior
• Other Study ID Numbers: NUDGE-FLU-CHRONIC-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No