RotaTeq® was 83.4% (95% CI 25.5, 98.2) efficacious in
the first year of life against severe rotavirus gastroenteritis (Vesikari score ≥ 11) and 34.4% (95% CI 5.3, 54.6) efficacious in preventing acute gastroenteritis associated with severe dehydration in the home setting. These differences highlight the need to critically evaluate the degree to which outcome measures and the tools BMS-907351 supplier to measure them are tuned to the population being studied. The preceding example also illustrates why comparisons of point estimates of efficacy alone provide an incomplete assessment of vaccine performance. Absolute disease rates and case reductions are more relevant measures of the public health impact of vaccines. This concept was endorsed by an international panel of experts convened in 2007, prior to the release of data from the rotavirus vaccine trials in developing countries [19]. Using the example above in Kenya, rotavirus vaccines prevented an estimated 3.3 cases per 100 child-years of severe rotavirus gastroenteritis, as defined by the Vesikari score and measured at health facilities, and 19
cases per 100 child-years of acute gastroenteritis with severe dehydration as defined by IMCI criteria and measured in the home [18]. This illustrates the importance of outcome definition, both from the perspective of comparisons, but also from the perspective of public health value. In rural Africa, prevention PF 01367338 of home cases of dehydration may be a more relevant measure of prevention as children have limited access to care, and thus the use of different outcome definitions can provide a more complete assessment old of disease reduction afforded by vaccines [18]. It will be important to report incidence rates in placebo and vaccine groups for a number of outcomes in trials of new rotavirus vaccines, again with an
understanding of how differences in case ascertainment and case definition could affect those incidence rates. Age is an important influencer of vaccine immunogenicity, with immune responses to vaccine generally improving with age. It is difficult to determine whether the lower immune responses reflect an immature immune system, or interference by high concentrations of maternal antibody that wane over time. What is known is that the high levels of serum neutralizing antibody against the human rotavirus serotypes in the RotaTeq® vaccine measured before vaccination, and thus presumed to be maternal antibody, has only been observed in the low resource settings of Africa and Asia [9]. Additional factors that could impact point estimates of efficacy are shown in Table 1. Some are difficult to quantify, and a full description of each of these parameters may not always be provided in published manuscripts. For example, while pivotal studies for licensure generally have strict inclusion criteria, the Rotarix® and RotaTeq® trials in Africa and Asia had more lenient inclusion criteria.