immunization schedule. This approach would also provide information about extreme outcomes or the 95th percentile of predicted outbreak sizes (Park et al., 2009; Rohani et al., 2009). Examination of sensitivity involves extensive repetition of the model simulation as a critical parameter of interest (e.g., the efficacy of the first dose of diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed administered at 3 months of age) is systematically varied.

The development, appropriate parameterization, and scrutiny of mechanistic transmission models have been adopted by a number of governmental agencies, and this process has been influential for determination of the implementation of specific immunization practices in countries such as the United Kingdom. In 2002, for example, Edmunds et al. used an approach similar to that outlined here to examine the potential cost-effectiveness of introduction of an acellular pertussis booster vaccine to the schedule in England and Wales (Edmunds et al., 2002). Similarly, Jit et al. (2008) carried out extensive analyses of detailed transmission models to inform the policy decision of the government of the United Kingdom on the effectiveness of routine vaccination of 12-year-old schoolgirls against human papillomavirus. Other examples include identification of the optimal targeting of age groups to contain the influenza pandemic (Medlock and Galvani, 2009), as well as pinpointing the most effective immunization schedule for meningococcal serogroup C (Trotter and Edmunds, 2006).

CONCLUSIONS

The committee deliberated on many potential research approaches and worked to determine which were feasible, ethical, and cost-effective. The commissioned paper in Appendix D helped identify methods that could be considered. Many questions can be answered by use of the methods described above, although they are not currently well integrated.

Chapter 7 summarizes the committee’s judgment on its statement of task. Setting of priorities for research will be challenging. For example, the committee does not recommend a study comparing the recommended immunization schedule and no immunization at this time because a high-quality randomized trial is not ethical and a prospective observational study could be complex, lengthy, and expensive and would potentially provide inconclusive results about key health outcomes after immunization. Thus, the committee proposes establishment of a process for setting priorities incorporating epidemiological and other evidence (on the basis of formal systematic reviews), biological plausibility, feasibility, and stakeholder concerns.



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