Conclusions about Research Methods

Vaccine safety is critically important, but a determination of safety is ultimately a value judgment. For example, some might believe that a serious adverse event that occurs once in 1 million doses is “safe enough” relative to the benefit of preventing a serious disease, whereas others may consider that risk unacceptably high. The committee did not set a specific numerical target or goal for what should be considered “safe enough.” Instead, based on the literature, the committee made a judgment that failed to link adverse effects to schedule exposures or multiple immunizations, concluding that there is no evidence that the schedule is not safe.

The committee identified four broad research questions of interest to stakeholders (Box S-2) and discussed general research approaches that could be used to address these questions. Setting of priorities for research will be challenging. The committee proposes a process for setting research priorities that incorporates epidemiological and other evidence (formal systematic reviews), biological plausibility, feasibility, and stakeholder concerns. Before HHS agencies, such as CDC, FDA, the National Institutes of Health, and NVPO, initiate further research on the entire immunization schedule, a thorough review of the biological plausibility of the association of a particular outcome with an aspect of the immunization schedule should be conducted.

Recommendation 6-1: The committee recommends that the Department of Health and Human Services incorporate study of the safety of the overall childhood immunization schedule into its processes for setting priorities for research, recognizing stakeholder concerns, and establishing the priorities on the basis of epidemiological evidence, biological plausibility, and feasibility.

The decision to initiate further studies should depend on the evaluation of three considerations that the committee identified through its review of stakeholder concerns and scientific findings:

  1. epidemiological evidence of potential adverse health outcomes associated with elements of the immunization schedule (such as postmarketing signals or indications of an elevated risk from observational studies);
  2. biological plausibility supporting hypotheses linking specific aspects of the immunization schedule with particular adverse health outcomes; and
  3. expressed stakeholder concerns about the immunization schedule’s safety, which should initiate efforts to explore the previous two considerations.


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