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Background  Adult and adolescent vaccination rates are far below coverage targets in the United States. Our objective was to identify the most influential factors related to vaccine uptake among adults, adolescents, and parents of adolescents (parents) in the United States.    Methods  We used a fractional factorial design to create a binary choice survey to evaluate preferences for vaccination. The national survey was fielded to a sample of adults, adolescents ages 13–17 years, and parents, using a national probability-based online research panel in November 2015. Respondents were presented with 5 profiles of a hypothetical vaccine and asked in a series of questions whether they would accept each vaccine. We analyzed the binary choice data using logistic regression in STATA v13 (College Station, TX) to calculate the odds that a participant would choose to accept the vaccine.    Results  We received completed responses from 334 (51%) of 652 adults, 316 (21%) of 1516 adolescents, and 339 (33%) of 1030 parents. Respondents were generally representative of the U.S. population. Vaccine effectiveness was the most influential factor in the choice to vaccinate for all groups. Other most influential factors were primary care provider (PCP) recommendation and the out-of-pocket cost of the vaccine. Other factors such as risk of illness, risk of vaccine side effects, vaccination location, and time for vaccination were not important in the decision to get vaccinated.    Conclusions  Adults, adolescents, and parents are most sensitive to vaccine effectiveness, PCP recommendation, and out-of-pocket cost for vaccination in their decision to get vaccinated. Strong PCP recommendations that focus on vaccine effectiveness and health care policies that minimize out-of-pocket costs for vaccinations may increase vaccine uptake by adults and adolescents.    Electronic supplementary material  The online version of this article (10.1186/s41687-019-0135-0) contains supplementary material, which is available to authorized users.

Use of a choice survey to identify adult, adolescent and parent preferences for vaccination in the United States