caa a22 4500 605533776 CHVBK 20210128100839.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10928-015-9427-z doi (NATIONALLICENCE)springer-10.1007/s10928-015-9427-z Biomarker- versus drug-driven tumor growth inhibition models: an equivalence analysis [Elektronische Daten] [Maria Sardu, Italo Poggesi, Giuseppe De Nicolao] The mathematical modeling of tumor xenograft experiments following the dosing of antitumor drugs has received much attention in the last decade. Biomarker data can further provide useful insights on the pathological processes and be used for translational purposes in the early clinical development. Therefore, it is of particular interest the development of integrated pharmacokinetic-pharmacodynamic (PK-PD) models encompassing drug, biomarker and tumor-size data. This paper investigates the reciprocal consistency of three types of models: drug-to-tumor, such as established drug-driven tumor growth inhibition (TGI) models, drug-to-biomarker, e.g. indirect response models, and biomarker-to-tumor, e.g. the more recent biomarker-driven TGI models. In particular, this paper derives a mathematical relationship that guarantees the steady-state equivalence of the cascade of drug-to-biomarker and biomarker-to-tumor models with a drug-to-tumor TGI model. Using the Simeoni TGI model as a reference, conditions for steady-state equivalence are worked out and used to derive a new biomarker-driven model. Simulated and real data are used to show that in realistic cases the steady-state equivalence extends also to transient responses. The possibility of predicting the drug-to-tumor potency of a new candidate drug based only on biomarker response is discussed. Springer Science+Business Media New York, 2015 PK-PD models nationallicence Causal pathways nationallicence Biomarkers nationallicence Tumor growth inhibition nationallicence Xenograft experiments nationallicence Simeoni model nationallicence Sardu Maria Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy aut Poggesi Italo Clinical Pharmacology & Pharmacometrics, Janssen Research & Development, 2340, Beerse, Belgium aut De Nicolao Giuseppe Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 611-626 1567-567X 42:6<611 2015 42 10928 https://doi.org/10.1007/s10928-015-9427-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9427-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sardu Maria Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy aut NATIONALLICENCE 700 1- Poggesi Italo Clinical Pharmacology & Pharmacometrics, Janssen Research & Development, 2340, Beerse, Belgium aut NATIONALLICENCE 700 1- De Nicolao Giuseppe Dipartimento di Ingegneria Industriale e dell'Informazione, Università di Pavia, Via Ferrata 1, 27100, Pavia, Italy aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/6(2015-12-01), 611-626 1567-567X 42:6<611 2015 42 10928