Some extensions in continuous models for immunological correlates of protection

Area of Science:

• Biostatistics
• Immunology
• Vaccinology

Background:

• A scaled logit model previously estimated the link between immunological assays and disease protection.
• This model assumed fixed exposure probability and assay-dependent protection.

Purpose of the Study:

• To investigate extensions of the scaled logit model for improved quantification of vaccine-induced protection.
• To explore alternative protection curve functions, case-cohort designs, and variance estimation methods.

Main Methods:

• Evaluated alternative protection curve functions and their impact on model fit.
• Assessed the utility of case-cohort designs and compared variance estimation approaches.
• Developed criteria for model evaluation and utility assessment, applied to 16 vaccine trial datasets.

Main Results:

• Alternative protection curve functions enhanced model evaluation across all datasets.
• Bootstrap estimates of precision were superior to observed information-based standard errors.
• Case-cohort designs generally maintained precision, and utility measures were identified.

Conclusions:

• The original scaled logit model can be refined for better performance.
• Proposed evaluation criteria effectively identify well-fitting models and useful results.
• The developed methods offer a robust toolkit for analyzing immunological assay-protection relationships.