viewed briefly below) and potential constraints from small sample sizes on the investigation of differences between men and women in risk factors for adverse events that occur at the time of vaccination (described in Chapter 5 and recapitulated below). Although the research program also lacks satisfactory plans for investigating adverse health effects that might be rare or become evident many years after vaccination, the committee has seen no evidence that such studies should be a high priority. These limitations do not alter the committee’s conclusion that the CDC research program as planned includes most of the studies needed to provide a strong and appropriate response to the congressional mandate.
When considered in its entirety, however, the CDC anthrax vaccine research program includes elements that the committee considers to be of lower priority, and some that should not be carried out as planned (see Table 7-1). These concerns have been detailed in chapters 4, 5, and 6 and are summarized below.
With respect to the tasks specifically outlined in the congressional mandate, CDC’s research response is generally complete and appropriate.
When considered as a whole, however, the research program has elements that are of low priority and other elements that are inappropriate and should not be carried out as planned.
Since the release of the interim report from this committee, CDC has devoted considerable and commendable effort to the development of the studies that make up the research plan. CDC grouped these studies into the categories of efficacy, safety, and acceptability. The committee’s assessments of the research objectives and studies planned in each of these categories are discussed in detail in the preceding chapters and are summarized below and in Table 7-1.
In making its assessments, the committee also considered the priority to be given to individual studies within the overall research program. While CDC designated all of the proposed studies as of high priority, the committee concluded that two efforts should be considered of the highest priority. One is the clinical trial and its related studies, which are aimed at identifying correlates of protection and establishing the optimal vaccination schedule and route of vaccine administration in terms of achieving a satisfactory immune response and minimizing the occurrence of adverse events. The other studies of highest priority are those exploiting the resource provided by the Defense Medical Surveillance System (DMSS) for generating and testing hypotheses about medically significant adverse events that might be associated with the anthrax vaccine. The committee also concluded that several studies had a low priority or should not be conducted at all.
Overall, the efficacy research program includes a strong set of studies (Human Clinical Trial, Nonhuman Primate Studies, Immune Correlates of Protection Studies) that are of high priority and are well designed to address many of the most important critical research questions and the congressional mandate. Aspects of the efficacy program pertaining to correlates of protection were viewed as particularly relevant, given that new anthrax vaccines are in development. Yet, the committee also notes important limitations of the research on the efficacy of AVA. Most importantly, the program lacks studies of passive protection in rhesus macaques. The committee views these studies as a high priority. They are necessary to determine the level of antibody required to achieve protection from disease caused by anthrax spores (see Chapter 4). The committee also notes the need for studies to evaluate the effect of inoculum size on the protection afforded by AVA. Such studies would be a natural follow-up to studies of passive protection that determined protective levels of antibodies. Their importance was made clear by the bioterrorist actions in the fall of 2001.