A method to address between-subject heterogeneity for identification of principal surrogate markers in repeated low-dose challenge HIV vaccine studies.

ABSTRACT: Repeated low-dose challenge designs in nonhuman primate studies have recently received attention in the literature as a means of evaluating vaccines for HIV prevention and identifying immune surrogates for their protective effects. Existing methods for surrogate identification in this type of study design rely on the assumption of homogeneity across subjects (namely, independent infection risks after each challenge within each subject and conditional on covariates). In practice, random variation across subjects is likely to occur because of unmeasured biologic factors. Failure to account for this heterogeneity or within-subject correlation can result in biased inference regarding the surrogate value of immune biomarkers and underpowered study designs for detecting surrogate endpoints. In t

SUBMITTER: Spieker AJ 

PROVIDER: S-EPMC5669638 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature