Can Flu Shot Nudges Lead to Fewer COVID Vaccinations?

Electronic letters encouraging influenza vaccination may have had the unintended consequence of decreasing COVID-19 vaccination rates, according to a prespecified secondary analysis of the Danish NUDGE-FLU trial.

Among nearly 700,000 adults ages 65 and older, the receipt of nine different intervention letters focused on increasing influenza vaccination uptake reduced the likelihood of receiving a COVID vaccine compared with usual care (86.16% vs 86.52%; P<0.001), reported Tor Biering-Sørensen, MD, MSc, MPH, PhD, of Copenhagen University Hospital – Herlev and Gentofte in Hellerup, Denmark, and colleagues in JAMA Network Open.

“To our knowledge, this is the first evidence in the context of a randomized clinical trial suggesting that implementation strategies promoting one form of vaccination may have unintended consequences on the uptake of other preventative interventions,” Biering-Sørensen and colleagues wrote.

However, Amesh Adalja, MD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, told MedPage Today that these results lack clinical significance.

“I don’t think that this is a really clinically significant finding as the absolute difference is so small. It does not make clinical sense, so I question whether this was a spurious finding (even though it had statistical significance) and does not really have face validity. I have not seen this phenomenon in my own practice,” Adalja noted.

The authors acknowledged that “even though the observed absolute decrease in COVID-19 vaccination was only modest and the statistical significance of our findings may have been primarily due to a large sample size, our findings serve as an important reminder that close coordination with other public health efforts and contemplating potential off-target consequences should be considered integral when designing specific public health messaging campaigns.”

“While individual off-target effects may be small in magnitude, population-wide implementation of such campaigns can potentially result in large-scale consequences,” they added. “Randomized trials of public health messaging and other implementation interventions should be greatly encouraged, and potential unintended consequences should be prospectively monitored in future trials.”

The NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) trial was conducted during the 2022-2023 influenza season in adults ages 65 and up in Denmark and sought to determine whether patient reminders (nine different electronic letters) to be vaccinated for influenza would increase vaccination rates compared with usual care. In their primary analysis, they found that electronic letters emphasizing potential cardiovascular benefits of influenza vaccination and repeated messaging increased influenza vaccination rates by approximately 1 percentage point.

Among the 964,870 participants in NUDGE-FLU, mean age was 73.8, 51.5% were women, and 87.7% received the COVID vaccine during the 2022-2023 season.

In this prespecified analysis, Biering-Sørensen and colleagues included data from 691,820 participants who received usual care or nine different electronic letters, which were designed using behavioral science principles and delivered through the governmental Danish electronic letter system. Among these participants, 86.3% received the COVID vaccine.

Of note, the two letters that were successful in increasing influenza vaccination rates did not significantly reduce COVID vaccination rates: the cardiovascular gain-framing letter (P=0.20) and the repeated letter (P=0.59).

The researchers reported no differences in clinical outcomes between participants who received any intervention letter and usual care. Laboratory-confirmed COVID infection occurred in 2.78% of patients who received any letter and 2.77% of those who received usual care (P=0.62), and hospitalization for COVID occurred in 0.30% of both groups (P=0.61).

Limitations to the study included the limited direct generalizability of the results to other health systems outside of Denmark, and the fact that the observed statistical significance may be primarily due to the large sample size.

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