Rights statement: 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. 2021; 20: 272– 281. 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.
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Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Assessing goodness-of-fit for evaluation of dose-proportionality
AU - Wolfsegger, M.J.
AU - Bauer, A.
AU - Labes, D.
AU - Schütz, H.
AU - Vonk, R.
AU - Lang, B.
AU - Lehr, S.
AU - Jaki, T.F.
AU - Engl, W.
AU - Hale, M.D.
N1 - 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. 2021; 20: 272– 281. 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.
PY - 2021/3/31
Y1 - 2021/3/31
N2 - 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.
AB - 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.
KW - dose-proportionality
KW - linear pharmacokinetics
KW - visual predictive checks
U2 - 10.1002/pst.2074
DO - 10.1002/pst.2074
M3 - Journal article
VL - 20
SP - 272
EP - 281
JO - Pharmaceutical Statistics
JF - Pharmaceutical Statistics
SN - 1539-1604
IS - 2
ER -