The objective is to (1) inform the audience about pharmacometrics (PMX) opportunities in vaccine discovery and development (D&D), and (2) to motivate, by examples, PMX practitioners to impact vaccine D&D.
Prophylactic vaccines are safe and effective and have made an immense contribution to human and animal health . Pharmacometrics (PMX) has only recently been introduced to vaccine discovery and development, and is now becoming fully integrated into, and impactful on decision-making. This has resulted in better scientific understanding, increased POS, substantial savings, and other benefits that have been seen in the other therapeutic areas that have adopted PMX. The impact of this work has included go and no-go decisions, design of efficient pre-clinical and clinical trials, integration of preclinical and clinical data, quantitative prediction for go/no-go and dose-level decisions, and integration of data across multiple trials for more informed decision-making. The methods used include QSP modelling, trial simulation, Bayesian inference, and model-based meta-analyses (“comparator modelling”).
The presentation will start with a background on vaccine discovery and development (contrasting with other therapeutic areas) including a brief overview of: the risk/benefit considerations in vaccines, the choices and uses of biomarkers to mitigate risk, vaccine terminology, the immune system, and vaccine platforms (DNA, protein, VLP, etc.). This will be followed by examples across the spectrum of applications from discovery through development and across the many kinds of decisions impacted and methods used. These will include
* An application of M&S that supported both Go and No-Go decisions
* An application of M&S that increased power in trial design while saving considerable cost by optimizing sampling of subjects’ disease state.
* An application of M&S providing a novel phase 3 endpoint substantially increasing power of a proposed trial design
Conclusions/Take home message
Application of PMX to vaccine D&D has developed into an opportunity to impact human health and to develop innovative PMX methods applicable to other areas.