administered at a single visit. Even though each new vaccine is evaluated in the context of the overall immunization schedule that existed at the time of review, individual elements of the schedule are not evaluated once it is adjusted to accommodate a new vaccine. Key elements of the immunization schedule—for example, the number, frequency, timing, order, and age at the time of administration of vaccines—have not been systematically examined in research studies.

The second major issue that the committee encountered during the review of the scientific literature was uncertainty over whether the scientific literature has addressed all health outcomes and safety concerns. The committee could not determine whether its list of health outcomes was complete or whether a more comprehensive system of surveillance might identify other outcomes of potential safety significance. In addition, the conditions of concern to some stakeholders, such as immunological, neurological, and developmental problems, are illnesses and conditions for which the etiology, in general, is not well understood. Further research on these conditions may clarify their etiologies.

Finally, the committee found that evidence from assessments of health outcomes in potentially susceptible subpopulations of children who may have an increased risk of adverse reactions to vaccines (such as children with a family history of autoimmune disease or allergies or children born prematurely) was limited and is characterized by uncertainty about the definition of populations of interest and definitions of exposures and outcomes. Most children who experience an adverse reaction to immunization have a preexisting susceptibility. Some predispositions may be detectable prior to vaccination; others, at least with current technology and practice, are not (IOM, 2012, p. 82).

In summary, to consider whether and how to study the safety and health outcomes of the entire childhood immunization schedule, the field needs valid and accepted metrics of the entire immunization schedule (the “exposure”) and clearer definitions of health outcomes linked to stakeholder concerns (the “outcomes”) in rigorous research that will ensure validity and generalizability.

Recommendation 5-1: To improve the utility of studies of the entire childhood immunization schedule, the committee recommends that the National Vaccine Program Office develop a framework that clarifies and standardizes definitions of

  • key elements of the schedule,
  • relevant health outcomes, and
  • populations that are potentially susceptible to adverse events.


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