The sample size included adjustment to allow for 20% of infants not being evaluable for the primary analysis. The higher MS-275 concentration than anticipated attack rates of S-RVGE during infancy alone, 3.3% in South Africa and 7.9% in Malawi, favored post hoc country-specific estimates of vaccine efficacy, despite not being planned a priori in the sample size calculations. Vaccine efficacy analysis was performed on the according-to-protocol (ATP) efficacy cohort, which included the first episode of any specified event occurring at least 2 weeks after the third dose of assigned study vaccine. For a specific event, vaccine

efficacy for each HRV group and for pooled HRV groups was primary computed as VE = vaccine efficacy = (1 − RR) × 100 = (1 − (ARV/ARU)) × 100, where ARU is the number of subjects reporting at least one event/total number of subjects in the placebo group; ARV is the number of subjects reporting at least one event/total number of subjects in the HRV vaccine group; Relative risk (RR) = ARV/ARU. The same transformation was used to derive the exact confidence interval (CI) boundaries from those obtained for the relative risk. selleck screening library The CI for the relative risk was based on the method described by Tang and Ng [19]. This primary analysis was complemented by: (i) two-sided Fisher’s exact test, (ii) vaccine

efficacy derived from a Cox regression model on the time to first event with censoring at end of study for

subjects without event (the model included the group as fixed effect), (iii) incidence rate in a group (P) was computed as the number of subjects reporting at least 1 event (n)/total follow-up time to a first event or censored at found end of study visit (T). The associated 95% CI was obtained considering that n followed a Poisson distribution with P × T parameter. The number of events prevented by 100 vaccinated infant-years was obtained from 100 times the difference in incidence rate. This associated CI was derived using the method by Zou and Donner [20]. For the immunogenicity analysis seropositivity/seroconversion rates and their exact 95% CI were tabulated and the geometric mean concentrations (GMCs) and their 95% CI were calculated. The 95% CI for the mean of log-transformed concentration was first obtained assuming that log-transformed concentrations were normally distributed with unknown variance. The 95% CI for the GMC was then obtained by exponential transformation of the 95% CI for the mean of log-transformed concentration. The analysis included the a priori comparison of the pooled HRV groups versus placebo group. In addition, an exploratory analysis was performed for following groups: each HRV group versus placebo group and the HRV_2D group versus HRV_3D group.