Relative Potency Estimation in Parallel-Line Assays – Method Comparison and Some Extensions

Abstract

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.