Electronic Nudges to Increase Influenza Vaccination in Patients With Chronic Diseases: A Randomized Clinical Trial

Abstract

Importance: Despite strong worldwide guideline recommendations, influenza vaccination rates remain suboptimal among young and middle-aged patients with chronic diseases. Effective scalable strategies to increase vaccination are needed.

Objective: To investigate whether electronically delivered letter-based nudges informed by behavioral science could increase influenza vaccination uptake among patients aged 18 to 64 years with chronic diseases.

Design, setting, and participants: Nationwide pragmatic registry-based randomized clinical implementation trial conducted between September 24, 2023, and May 31, 2024, enrolling all Danish citizens aged 18 to 64 years who met criteria for free-of-charge influenza vaccination in light of preexisting chronic disease. All trial data were sourced from nationwide administrative health registries.

Intervention: Randomized in 2.45:1:1:1:1:1:1 ratio to no letter (usual care) or 6 different behaviorally informed electronic letters.

Main outcomes and measures: The primary end point was receipt of influenza vaccination on or before January 1, 2024, assessed in 7 prespecified coprimary comparisons (all intervention groups pooled vs usual care and each individual intervention group vs usual care). Absolute risk difference in proportions and a crude relative risk were calculated for each comparison.

Results: A total of 299 881 participants (53.2% [159 454] female, median age, 52.0 [IQR, 39.8-59.0] years) were randomized. Compared with usual care, influenza vaccination rates were higher among those receiving any intervention letter (any intervention letter, 39.6% vs usual care, 27.9%; difference, 11.7 percentage points; 99.29% CI, 11.2-12.2 percentage points; P < .001). Each individual letter type significantly increased influenza vaccination with the largest effect sizes observed with a repeated letter sent 10 days after the initial letter (repeated letter, 41.8% vs usual care, 27.9%; difference, 13.9 percentage points; 99.29% CI, 13.1-14.7 percentage points; P < .001) and a letter emphasizing potential cardiovascular benefits of vaccination (cardiovascular gain, 39.8% vs usual care, 27.9%; difference, 11.9 percentage points; 99.29% CI, 11.1-12.7 percentage points; P < .001). Vaccination rates were improved across major subgroups.

Conclusions and relevance: In a nationwide randomized clinical implementation trial, electronically delivered letter-based nudges markedly increased influenza vaccination compared with usual care among young and middle-aged patients with chronic diseases. The results of this study suggest that simple, scalable, and cost-efficient electronic letter strategies may have substantial public health implications.

Trial registration: ClinicalTrials.gov Identifier: NCT06030739.

Figure 1.. Identification, Exclusion, and Randomization of Participants in the Trial

Eligible participants were randomized in a 2.45:1:1:1:1:1:1 ratio to either usual care or 6 different active groups, each receiving different behaviorally informed electronic letters nudging participants to make the decision to obtain influenza vaccination (letters are described in the Methods section). No exclusions were made after randomization and group assignment. Citizens may apply for an exemption from the electronic letter system to receive physical letters instead. Exemptions are granted for several reasons including physical or mental impairment and lack of computer/internet access.

Figure 2.. Results for Primary End Point of Influenza Vaccination Receipt

The primary end point was receipt of influenza vaccination on or before January 1, 2024. A total of 7 prespecified comparisons were made and adjusted for multiplicity with each comparison performed at an α level of .0071. Nominal 99.29% CIs are reported to maintain an overall α level of .05 for the primary end point. Unadjusted P values are shown. The primary analyses shown in this Figure do not account for censoring. In total, during follow-up for receipt of influenza vaccination, 1008 participants (0.3%) died and 382 participants (0.1%) emigrated. CV indicates cardiovascular.

Figure 3.. Results for 3 of 7 Comparisons for Secondary End Point of Time to Influenza Vaccination Receipts

The secondary end point was influenza vaccination modeled as a time-to-event outcome. Cumulative incidence curves were estimated using the Kaplan-Meier method. Time 0 was the date of initial intervention delivery for all participants (September 24, 2023). Participants were censored at end of follow-up (January 1, 2024), death, or emigration, whichever occurred first. The numbers at risk at baseline differ from the total number of randomized participants in each group due to censoring occurring on the first day of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). No violations of the proportional hazards assumption were found. A total of 7 prespecified comparisons were made and adjusted for multiplicity with each comparison performed at an α level of .0071. Nominal 99.29% CIs are reported to maintain an overall α level of .05 for the secondary end point. Unadjusted P values are shown.

Figure 4.. Results for 4 of 7 Comparisons for Secondary End Point of Time to Influenza Vaccination Receipts

The secondary end point details are reported in the caption to Figure 3. CV indicates cardiovascular; HR, hazard ratio.

Figure 5.. Primary End Point Across Prespecified Subgroups for Comparison of Any Intervention Letter vs Usual Care

We tested for homogeneous treatment effects across prespecified subgroups for the primary end point for the comparison of all intervention groups pooled vs usual care using binomial regression with identity link and interaction terms. Median age was 52.0 (IQR, 39.8-59.0) years. The P values shown are interaction P values.