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Alternatives to statistical decision trees in regulatory (eco-)toxicological bioassays

  • Regulatory Toxicology
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Abstract

The goal of (eco-) toxicological testing is to experimentally establish a dose or concentration–response and to identify a threshold with a biologically relevant and probably non-random deviation from “normal”. Statistical tests aid this process. Most statistical tests have distributional assumptions that need to be satisfied for reliable performance. Therefore, most statistical analyses used in (eco-)toxicological bioassays use subsequent pre- or assumption-tests to identify the most appropriate main test, so-called statistical decision trees. There are however several deficiencies with the approach, based on study design, type of tests used and subsequent statistical testing in general. When multiple comparisons are used to identify a non-random change against negative control, we propose to use robust testing, which can be generically applied without the need of decision trees. Visualization techniques and reference ranges also offer advantages over the current pre-testing approaches. We aim to promulgate the concepts in the (eco-) toxicological community and initiate a discussion for regulatory acceptance.

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Notes

  1. N.B. after peer-review another study investigated the robustness of the MLT-Dunnett for count data which is available as a pre-print: Hothorn and Kluxen (2020) Statistical analysis of no observed effect concentrations or levels in eco-toxicological assays with overdispersed count endpoints. https://doi.org/10.1101/2020.01.15.907881.

  2. Hothorn and Kluxen (2020) has become available in the meantime as a preprint, which investigates the MLT-Dunnett's robustness for count data.

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Correspondence to Felix M. Kluxen.

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Kluxen, F.M., Hothorn, L.A. Alternatives to statistical decision trees in regulatory (eco-)toxicological bioassays. Arch Toxicol 94, 1135–1149 (2020). https://doi.org/10.1007/s00204-020-02690-w

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  • DOI: https://doi.org/10.1007/s00204-020-02690-w

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