Challenges in comparing the safety of different vaccination schedules

As vaccine hesitancy has increased in the United States, various authors have begun proposing alternatives to the Advisory Committee on Immunization Practices’ recommended childhood immunization schedule. Because parents may believe the safety claims made by such authors, evaluations of the safety of alternative vaccination schedules are needed. However, comparing the safety of different vaccination schedules has numerous methodologic challenges. These challenges include defining vaccination history, defining safety, appropriately modeling interactions between vaccines, and appropriately handling age effects. Failure to properly address these challenges can result in biased results.

► Alternative immunization schedules are increasing in popularity.
► Comparing relative safety of recommended vs alternative schedules has challenges.
► One challenge is how to define exposure (vaccine level or schedule level).
► Other challenges are modeling outcomes, interactions, and age effects.
► These challenges would be present even in an ideal randomized trial.