Bayesian inference for prediction of survival probability in prime‐boost vaccination regimes

• Published in: Statistics in medicine 2024-02, Vol.43 (3), p.560-577
• Main Authors: Lu, Yuelin, Carlin, Bradley P., Seaman, John W.
• Format: Article
• Language: English
• Subjects: Bayes Theorem; Bayesian analysis; Bayesian hierarchical model; dose–response modeling; Ebola Vaccines - pharmacology; Ebola virus; Hemorrhagic Fever, Ebola - prevention & control; heterologous vaccination; Humans; Immunization, Secondary; Probability; Survival analysis; Vaccination; Vaccines
• ISSN: 0277-6715; 1097-0258
• DOI: 10.1002/sim.9972

We focus on Bayesian inference for survival probabilities in a prime‐boost vaccination regime in the development of an Ebola vaccine. We are interested in the heterologous prime‐boost regimen (unmatched vaccine deliverys using the same antigen) due to its demonstrated durable immunity, well‐tolerated safety profile, and suitability as a population vaccination strategy. Our research is motivated by the need to estimate the survival probability given the administered dosage. To do so, we establish two key relationships. Firstly, we model the connection between the designed dose concentration and the induced antibody count using a Bayesian response surface model. Secondly, we model the association between the antibody count and the probability of survival when experimental subjects are exposed to the Ebola virus in a controlled setting using a Bayesian probability of survival model. Finally, we employ a combination of the two models with dose concentration as the predictor of the survival probability for a future vaccinated population. We implement our two‐level Bayesian model in Stan, and illustrate its use with simulated and real‐world data. Performance of this model is evaluated via simulation. Our work offers a new application of drug synergy models to examine prime‐boost vaccine efficacy, and does so using a hierarchical Bayesian framework that allows us to use dose concentration to predict survival probability.