Relative Potency Estimation in Parallel-Line Assays - Method Comparison and Some Extensions
نویسندگان
چکیده
This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Relative potency estimations in both multiple parallel-line and slope-ratio assays involve construction of simultaneous confidence intervals for ratios of linear combinations of general linear model parameters. The key problem here is that of determining multiplicity adjusted percentage points of a multivariate t-distribution, the correlation matrix R of which depends on the unknown relative potency parameters. Several methods have been proposed in the literature on how to deal with R. In this article, we introduce a method based on an estimate of R (also called the plug-in approach) and compare it with various methods including conservative procedures based on probability inequalities. Attention is restricted to parallel-line assays though the theory is applicable for any ratios of coefficients in the general linear model. Extension of the plug-in method to linear mixed effect models is also discussed. The methods will be compared with respect to their simultaneous coverage probabilities via Monte Carlo simulations. We also evaluate the methods in terms of confidence interval width through application to data on multiple parallel-line assay.
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