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Assessing goodness‐of‐fit for evaluation of dose‐proportionality
Author(s) -
Wolfsegger Martin J.,
Bauer Alexander,
Labes Detlew,
Schütz Helmut,
Vonk Richardus,
Lang Benjamin,
Lehr Stephan,
Jaki Thomas F.,
Engl Werner,
Hale Michael D.
Publication year - 2020
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.2074
Subject(s) - proportionality (law) , goodness of fit , computer science , statistics , medical physics , medicine , mathematics , law , political science
SUMMARY 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.