A New Bliss Independence Model to Analyze Drug Combination Data.
J Biomol Screen
; 19(5): 817-21, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24492921
ABSTRACT
The Bliss independence model is widely used to analyze drug combination data when screening for candidate drug combinations. The method compares the observed combination response (Y(O)) with the predicted combination response (Y(P)), which was obtained based on the assumption that there is no effect from drug-drug interactions. Typically, the combination effect is declared synergistic if Y(O) is greater than Y(P). However, this method lacks statistical rigor because it does not take into account the variability of the response measures and can frequently cause false-positive claims. In this article, we introduce a two-stage response surface model to describe the drug interaction across all dose combinations tested. This new method enables robust statistical testing for synergism at any dose combination, thus reducing the risk of false positives. The use of the method is illustrated through an application describing statistically significant "synergy regions" for candidate drug combinations targeting epidermal growth factor receptor and the insulin-like growth factor 1 receptor.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Combinação de Medicamentos
/
Interações Medicamentosas
/
Modelos Químicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Biomol Screen
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos