Assessing goodness-of-fit for evaluation of dose-proportionality

Wolfsegger, M.J. and Bauer, A. and Labes, D. and Schütz, H. and Vonk, R. and Lang, B. and Lehr, S. and Jaki, T.F. and Engl, W. and Hale, M.D. (2020) Assessing goodness-of-fit for evaluation of dose-proportionality. Pharmaceutical Statistics. ISSN 1539-1604

[img]
Text (Manuscript_Dose_proportionality_23JULY_clean)
Manuscript_Dose_proportionality_23JULY_clean.pdf - Accepted Version
Restricted to Repository staff only until 15 October 2021.
Available under License Creative Commons Attribution-NonCommercial.

Download (1MB)

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.

Item Type:
Journal Article
Journal or Publication Title:
Pharmaceutical Statistics
Additional Information:
This is the peer reviewed version of the following article: Wolfsegger, MJ, Bauer, A, Labes, D, et al. Assessing goodness‐of‐fit for evaluation of dose‐proportionality. Pharmaceutical Statistics. 2020; 1– 10. https://doi.org/10.1002/pst.2074 which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/pst.2074 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2736
Subjects:
ID Code:
148764
Deposited By:
Deposited On:
04 Nov 2020 11:25
Refereed?:
Yes
Published?:
Published
Last Modified:
04 Nov 2020 11:25