immunized children. Experts who addressed the committee pointed not to a body of evidence that had been overlooked but rather to the fact that existing research has not been designed to test the entire immunization schedule.
The committee believes that although the available evidence is reassuring, studies designed to examine the long-term effects of the cumulative number of vaccines or other aspects of the immunization schedule have not been conducted. Nevertheless, in its literature review, the committee found useful designs for studies to measure exposures and outcomes and identified strategies for expanding or adapting conventional study designs to clearly address whether any adverse health outcomes are associated with the overall immunization schedule.
Moving from an analysis of stakeholder concerns and the limited scientific evidence about the association between the immunization schedule and adverse events to recommendation of specific research methods and study designs to address that association is an ambitious task in light of the complexity and changing nature of the recommended immunization schedule. Variables such as the number of doses, the age of administration, and the amount of time between doses permit the examination of a large number of potential research questions. Among the many questions about the current immunization schedule that could be posed, the committee parsed the phrase “this question” in Part 2 of the statement of task (Box S-1) into four broad research questions of interest to stakeholders. These are identified in Box S-2.
The committee broadly considered several general research strategies that might be used to address these questions: randomized controlled trials (RCTs), prospective and retrospective observational studies, animal models, and secondary analyses of existing data.
Randomized Controlled Trials
When it is possible to randomize study participants, the RCT is widely acknowledged to be the preferred study design for determining cause and effect. RCTs are currently used as part of the FDA approval process to evaluate the safety and effectiveness of individual vaccines in the context of the recommended immunization schedule. Although this is the strongest type of study design, the committee concluded that costs, the large number of participants that would be required, ethical concerns, and other factors make it an inappropriate design for addressing the research questions at hand.
RCTs require participants to be randomly assigned to a study group.