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Updated: May 7, 2026

Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
A comparison of statistical methods for combining relative bioactivities from parallel line bioassays
Thembile Mzolo1, Marga Hendriks, Edwin van den Heuvel
1University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract:
This paper compares the ordinary unweighted average, weighted average, and maximum likelihood methods for estimating a common bioactivity from multiple parallel line bioassays. Some of these or similar methods are also used in meta-analysis. Based on a simulation study, these methods are assessed by comparing coverage probabilities of the true relative bioactivity and the length of the confidence intervals computed for these methods. The ordinary unweighted average method outperforms all statistical methods by consistently giving the best coverage probability but with somewhat wider confidence intervals. The weighted average methods give good coverage and smaller confidence intervals when combining homogeneous bioactivities. For heterogeneous bioactivities, these methods work well when a liberal significance level for testing homogeneity of bioactivities is used. The maximum likelihood methods gave good coverage when homogeneous bioactivities were considered. Overall, the preferred methods are the ordinary unweighted average and two weighted average methods that were specifically developed for bioassays.
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