Fostering Culture and Optimizing Organizational Structure for Implementing Model‐Based Drug Development

Abstract

Model-based drug development (MBDD) is a promising approach to improve decision making in drug development. The pharmaceutical industry has made substantial progress from engaging in empirical decision making to increasingly using pharmacometrics (ie, modeling and simulation [M&S]) as a quantitative decision-making tool. Focusing on culture and an organizational structure perspective, this commentary summarizes experiences and vision from industry M&S leaders on implementing MBDD. A culture for MBDD needs to have wide acceptance of MBDD, enhanced decision making with probability-based evidence and transparent rationale, quantitative impact metrics, and a brand that emphasizes cross-disciplinary collaboration and ownership. An organizational structure for MBDD needs to have a dedicated pharmacometrics function, fine balance between quick wins and impact on long-term R&D goals, and collaborative MBDD teams among clinical pharmacologists, statisticians, pharmacometricians, and clinicians. Pharmaceutical companies with these characteristics are prepared to fully embrace and implement MBDD.

Modeling and simulation in pediatric drug therapy: Application of pharmacometrics to define the right dose for children

“…The application of quantitative pharmacology and pharmacometrics was first introduced in adult drug development programs. The goal of quantitative model‐based drug development (QMBDD) is to aid efficient drug development, regulatory decision making, and rational drug treatment in patients . In recent years, with the advent of European Medicines Agency (EMA)'s required pediatric investigational plan and the US Food and Drug Administration (FDA)'s pharmacometrics initiative a paradigm shift in the design and conduct of pediatric clinical drug studies has been initiated …”

Quantitative Evaluation and Prediction of Drug Effects and Toxicological Risk Using Mechanistic Multiscale Models

“…Computational models will increasingly help to accompany, guide, and accelerate the entire drug development process by integrating data developed at different stages into the model hence providing a rational and quantitative basis for decisions 73,74. In our opinion, particularly the combination of whole‐body models and detailed mechanistic models of drug metabolism and cellular metabolism resulting in multiscale models can accelerate drug development processes tremendously.…”

Mathematical modeling of tumor growth and tumor growth inhibition in oncology drug development

“…This approach will increase efficiency in drug development, eventually leading to better decision-making due to the integration of the wealth of information available [71]. In turn, research and development expenditures associated with conducting unnecessary trials will be saved [72]. This is an exciting time for modeling in oncology.…”