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High-dose influenza vaccine is recommended for U.S. adults older than 65, but the supporting data are relatively weak, consisting largely of findings from small observational studies and meta-analyses. A sufficiently powered randomized trial would require tens of thousands of participants; such a trial would be prohibitively labor intensive and expensive in the U.S., but perhaps would be less so in a country where national health insurance facilitates clinical data collection.
Danish researchers decided to see if their national health registry might supply enough clinical information to make such a giant trial feasible. In an industry-supported pilot project, conducted during the 2021–2022 flu season, they randomized more than 12,000 Danish …