• Niklas Dyrby Johansen, Muthiah Vaduganathan, Ankeet S Bhatt, Daniel Modin, Safia Chatur, Brian L Claggett, Kira Hyldekær Janstrup, Carsten Schade Larsen, Lykke Larsen, Lothar Wiese, Michael Dalager-Pedersen, Lars Køber, Scott D Solomon, Pradeesh Sivapalan, Jens Ulrik Stæhr Jensen, Cyril Jean-Marie Martel, Tyra Grove Krause, and Tor Biering-Sørensen.
• Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.
• JAMA. 2024 Oct 11.

ImportanceDespite 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.ObjectiveTo 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 ParticipantsNationwide 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.InterventionRandomized 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 MeasuresThe 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.ResultsA 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT06030739.

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