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Physiologically based pharmacokinetic (PBPK) models and quantitative systems pharmacology (QSP) models are built on prior knowledge, including (patho-)physiology, and pharmacology. The independent representations of drug and system specific parameters allow for extrapolation to scenarios beyond observation. This can help decision makers with informing biomarker strategies and early prediction of clinical outcome. Meet Erik Sjögren and Tobias Kanacher, with long experiences as consultants in this area. After defining how these modeling techniques work, they describe how they are now supporting clients in their daily work.