Endpoints were measured and evaluated independently two times, and then they were compared to identify potential discrepancies.
For each RCD and NCD chemical, the following endpoints driving classification were determined and evaluated: corneal opacity (CO), iritis (IR), conjunctiva chemosis (CC), conjunctiva redness (CR), and days to clear.
Two endpoints were evaluated: renal fibrosis and renal mononuclear cell infiltration.
In addition, CRP was not identified as a contributor in the panel of biomarkers identified as predictive of clinical response for any of the endpoints evaluated.
In addition to the primary and secondary endpoints, we evaluated patient demographics and tried to identify potential confounders.
Relationships between percentage change in peak VO2 from baseline to end of treatment and other endpoints were evaluated using correlation coefficients and regression analyses.
Safety and immunogenicity endpoints were evaluated in a double-blind manner as the investigators and their parent(s)/guardian(s) were unaware which vaccine was administered to a particular child.
Relationships with mortality and other endpoints were evaluated for the following variables: severity scores; age; sex; ICU and hospital stay lengths; co-morbidities; presence at admission of sepsis, severe sepsis or septic shock; use of invasive or noninvasive ventilation, inotropic agents, glucocorticoids or hemodialysis-hemofiltration; and recovered pathogens.
By enrolling this second cohort it was possible to estimate efficacy for a more upstream endpoint and to evaluate how it correlated with efficacy against clinical malaria in Cohort 1. Participants in Cohort 2 were followed up through both active detection of infection (ADI) and PCD.
During the formal interim analysis, an analysis of the utility data so far obtained will also be performed to revise the estimates of the power to detect the composite QALY endpoint and to evaluate possible refinements in the trial design as a result.
