1. Assessing goodness‐of‐fit for evaluation of dose‐proportionality
- Author
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Stephan Lehr, Detlew Labes, Benjamin Lang, Hale Michael Don, Helmut Schütz, Thomas Jaki, Alexander Bauer, Richardus Vonk, Werner Engl, and Martin J. Wolfsegger
- Subjects
Pharmacology ,Statistics and Probability ,Dose-Response Relationship, Drug ,Computer science ,01 natural sciences ,010104 statistics & probability ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Dose proportionality ,Goodness of fit ,Econometrics ,Humans ,Table (database) ,Computer Simulation ,Pharmacology (medical) ,030212 general & internal medicine ,0101 mathematics - Abstract
For the clinical development of a new drug, the determination of dose-proportionality is an essential part of the pharmacokinetic evaluations, which may provide early indications of non-linear pharmacokinetics and may help to identify sub-populations with divergent clearances. Prior to making any conclusions regarding dose-proportionality, the goodness-of-fit of the model must be assessed to evaluate the model performance. We propose the use of simulation-based visual predictive checks to improve the validity of dose-proportionality conclusions for complex designs. We provide an illustrative example and include a table to facilitate review by regulatory authorities.
- Published
- 2020