TY  - JOUR
AU  - Holland-Letz, Tim
AU  - Leibner, Alexander
AU  - Kopp-Schneider, Annette
TI  - Modeling dose-response functions for combination treatments with log-logistic or Weibull functions.
JO  - Archives of toxicology
VL  - 94
IS  - 1
SN  - 1432-0738
CY  - Heidelberg
PB  - Springer
M1  - DKFZ-2019-02868
SP  - 197-204
PY  - 2020
N1  - #EA:C060#LA:C060# 2020 Jan;94(1):197-204
AB  - Dose-response curves of new substances in toxicology and related areas are commonly fitted using log-logistic functions. In more advanced studies, an additional interest is often how these substances will behave when applied in combination with a second substance. Here, an essential question for both design and analysis of these combination experiments is whether the resulting dose-response function will still be a member of the class of log-logistic functions, and, if so, what function parameters will result for the combined substances. Different scenarios might be considered in regard to whether a true interaction between the substances is expected, or whether the combination will simply be additive. In this paper, it is shown that the resulting function will in general not be a log-logistic function, but can be approximated very closely with one. Parameters for this approximation can be predicted from the parameters of both ingredients. Furthermore, some simple interaction structures can still be represented with a single log-logistic function. The approach can also be applied to Weibull-type dose-response functions, and similar results are obtained. Finally, the results were applied to a real data set obtained from cell culture experiments involving two cancer treatments, and the dose-response curve of a combination treatment was predicted from the properties of the singular substances.
LB  - PUB:(DE-HGF)16
C6  - pmid:31786636
DO  - DOI:10.1007/s00204-019-02631-2
UR  - https://inrepo02.dkfz.de/record/148310
ER  -