Immunogenicity data from phase 1 vaccination trials can be challenging to interpret, particularly in seropositive groups and when numerous tests are employed. Researchers developed three statistical methods to characterize complex immunogenicity data (Youden index [YI] threshold, receiver-operating characteristic relative to baseline [ROC-B], and receiver-operating characteristic of post-dose levels [ROC-P]) by assessing the proportion of a study population that achieved values above thresholds. The YI approach computes a single threshold for each assay. To assess the degree of separation of post-dose values from a reference distribution, both ROC methods construct ROC curves for individual assays and surfaces for assay combinations; the ROC-B method uses overall predose values as the reference distribution, while the ROC-P method uses pooled post-dose values. All approaches were relevant to a seropositive population with overlapping baseline and post-dose measurement distributions and examined several test findings concurrently. When post-dose values were completely separated from baseline levels, as was usual in a seronegative population, the ROC-P technique was also relevant. Data from phase 1a research of respiratory syncytial virus vaccines made with and without an adjuvant in a seropositive group of people aged 60 years were used to illustrate these procedures.
All three methodologies offered a thorough evaluation of vaccination immunogenicity effects, with findings presented in clearly understandable forms. All approaches were suitable to a seropositive population with overlapping baseline and post-dose measurement distributions and may examine several test findings at the same time. When post-dose levels were completely isolated from baseline levels, as they were in a seronegative population, the ROC-P approach can be used. Data from phase 1a research of respiratory syncytial virus vaccines made with and without an adjuvant in a seropositive group of people aged 60 years was used to illustrate these procedures. All three methodologies offered a thorough examination of vaccine immunogenicity, with the data presented in clearly understandable formats.
The approaches exhibited antigen dosage response trend and adjuvant contribution to response in several assays separately and together in the example data, where excellent responses in test combinations (humoral and cellular) are crucial.
Reference:www.tandfonline.com/doi/full/10.1080/21645515.2018.1489191
