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Disease Progression Analysis: Towards Mechanism-Based Models

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Book cover Clinical Trial Simulations

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 1))

Abstract

Sustained disturbances of the biological homeostasis can result in chronic progressive diseases. The respective disease status as well as the corresponding effect of drug treatment on disease progression can be characterized at different levels of complexity, ranging from data-driven and descriptive to fully mechanistic approaches. Most of the currently employed disease progression models are mechanism-based and represent a mixture of these two extremes. Conceptually, mechanism-based disease progression models consist of three distinct parts: (1) a pharmacokinetic model to predict target exposure, (2) a pharmacodynamic model to characterize target binding, target activation, and transduction (receptor theory; dynamical system analysis), and (3) a disease model to characterize placebo response and disease progression. Once identified and validated, mechanism-based disease progression models can help understanding the behavior of the underlying disease system and, subsequently, support the identification of optimal dosing regimens using optimized clinical trial designs.

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Authors and Affiliations

  1. Leiden-Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Leiden, The Netherlands

    Meindert Danhof

Authors
  1. Stephan Schmidt
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  2. Teun M. Post
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  3. Massoud A. Boroujerdi
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  4. Charlotte van Kesteren
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  5. Bart A. Ploeger
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  6. Oscar E. Della Pasqua
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  7. Meindert Danhof
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Corresponding author

Correspondence to Meindert Danhof .

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Editors and Affiliations

  1. Department of Advanced Modeling & Simula, Janssen Research & Development, LLC, Route 202 S. 920, Raritan, 08869, New Jersey, USA

    Holly H. C. Kimko

  2. Dept. Biopharmaceutical Sciences, University of California, San Francisco, Parnassus Ave. 513, San Francisco, 94143-0446, California, USA

    Carl C. Peck

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Schmidt, S. et al. (2011). Disease Progression Analysis: Towards Mechanism-Based Models. In: Kimko, H., Peck, C. (eds) Clinical Trial Simulations. AAPS Advances in the Pharmaceutical Sciences Series, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7415-0_19

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