IMR Press / FBE / Volume 2 / Issue 1 / DOI: 10.2741/E88

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Efficient experiment design and nonparametric modeling of drug interaction

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1 Division of Biostatistics, University of Maryland Greenebaum Cancer Center and Department of Epidemiology and Preventive Medicine, 10 South Pine Street, MSTF Suite 261, Baltimore, MD 21201
2 Department of Mathematics, University of Maryland, College Park, MD 20742

*Author to whom correspondence should be addressed.

Academic Editor: William R. Greco

Front. Biosci. (Elite Ed) 2010, 2(1), 258–265; https://doi.org/10.2741/E88
Published: 1 January 2010
Abstract

The design and analysis of drug combination studies continue to be an area requiring further methodological developments. Faessel et al. (1998) studied the joint effects of the combinations of trimetrexate (TMQ) and the GARFT inhibitor AG2034 to inhibit the growth of HCT-8 human ileocecal adenocarcinoma cells. Their experiments provide a rich data resource to validate the performance of new experimental design and analysis methods for future experiments. In this paper, we first re-analyze the same data with a nonparametric model and briefly review the experimental design used in the original paper. By comparing the analysis results, we found that the fixed ratio design and the usage of the parametric model for estimating the interaction index are based on an assumption not supported by the data. We then show how the efficiency of the experiments would be improved had the maximal power experimental design based on uniform measures been used. The usage of the proposed maximal power experimental design is further supported by simulation studies.

Keywords
Additivity
Synergy
Dose-effect
Experimental Design
Interaction Index
Maximal Power Design
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