Robust benchmark dose determination based on profile score methods |
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Authors: | Gerda Claeskens Marc Aerts Geert Molenberghs Louise Ryan |
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Institution: | (1) Department of Statistics, Texas A&M University, College Station, TX, 77843, U.S.A.;(2) Biostatistics, Center for Statistics, Limburgs Universitair Centrum, B-3590 Diepenbeek, Belgium |
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Abstract: | We investigate several methods commonly used to obtain a benchmark dose and show that those based on full likelihood or profile likelihood methods might have severe shortcomings. We propose two new profile likelihood-based approaches which overcome these problems. Another contribution is the extension of the benchmark dose determination to non full likelihood models, such as quasi-likelihood, generalized estimating equations, which are widely used in settings such as developmental toxicity where clustered data are encountered. This widening of the scope of application is possible by the use of (robust) score statistics. Benchmark dose methods are applied to a data set from a developmental toxicity study. |
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Keywords: | clustered binary data generalized estimating equations likelihood ratio profile likelihood score statistic toxicology |
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