Detecting bliss synergy in in vivo combination studies with a tumor kinetic model.
bliss independence
drug combination
tumor kinetics
Journal
Pharmaceutical statistics
ISSN: 1539-1612
Titre abrégé: Pharm Stat
Pays: England
ID NLM: 101201192
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
25
10
2018
revised:
13
04
2019
accepted:
22
04
2019
pubmed:
30
5
2019
medline:
25
7
2020
entrez:
30
5
2019
Statut:
ppublish
Résumé
Linear models are generally reliable methods for analyzing tumor growth in vivo, with drug effectiveness being represented by the steepness of the regression slope. With immunotherapy, however, not all tumor growth follows a linear pattern, even after log transformation. Tumor kinetics models are mechanistic models that describe tumor proliferation and tumor killing macroscopically, through a set of differential equations. In drug combination studies, although an additional drug-drug interaction term can be added to such models, however, the drug interactions suggested by tumor kinetics models cannot be translated directly into synergistic effects. We have developed a novel statistical approach that simultaneously models tumor growth in control, monotherapy, and combination therapy groups. This approach makes it possible to test for synergistic effects directly and to compare such effects among different studies.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
688-699Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
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