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**Statistical evaluation of toxicological assays with zero or near-to-zero proportions or counts in the concurrent negative control group : a tutorial.** / Jaki, Thomas; Kitsche, Andreas; Hothorn, Ludwig A.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Jaki, T, Kitsche, A & Hothorn, LA 2014, 'Statistical evaluation of toxicological assays with zero or near-to-zero proportions or counts in the concurrent negative control group: a tutorial', *JP Journal of Biostatistics*, vol. 11, no. 1, pp. 1-32. <http://www.pphmj.com/abstract/8536.htm>

Jaki, T., Kitsche, A., & Hothorn, L. A. (2014). Statistical evaluation of toxicological assays with zero or near-to-zero proportions or counts in the concurrent negative control group: a tutorial. *JP Journal of Biostatistics*, *11*(1), 1-32. http://www.pphmj.com/abstract/8536.htm

Jaki T, Kitsche A, Hothorn LA. Statistical evaluation of toxicological assays with zero or near-to-zero proportions or counts in the concurrent negative control group: a tutorial. JP Journal of Biostatistics. 2014;11(1):1-32.

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title = "Statistical evaluation of toxicological assays with zero or near-to-zero proportions or counts in the concurrent negative control group: a tutorial",

abstract = "In toxicological studies interest often lies in proportions or counts for which an increase in the dose group over control indicates a safety risk. Additionally, the control group observes values that are zero or near-to-zero for endpoints characterizing pathological processes. In such instances, the comparison of dose groups versus control requires special attention as inference for ratio-to-control is infeasible or unstable and inference for difference-to-control is highly sensitive to the number of zeros or near-to-zero values. In practice, assays are commonly performed multiple times in a laboratory so that data of some historical controls are available. When the concurrent control values fall within a corresponding normal range, the evaluation is performed by comparing doses versus the concurrent control. If the data of the concurrent control are outside the normal range, a test versus the concurrent control has either an increased risk of a false-positive result or an increased risk of a false-negative result, depending on the direction of the deviation. In this work, we discuss a simple to use Williams-type approach for comparing against a mean historical value. The idea is illustrated on three examples and we show how the method can be implemented the statistical software package R.",

keywords = "count, proportion, near-to-zero, historical controls, poly-3 test, Williams trend test",

author = "Thomas Jaki and Andreas Kitsche and Hothorn, {Ludwig A}",

year = "2014",

language = "English",

volume = "11",

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journal = "JP Journal of Biostatistics",

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T1 - Statistical evaluation of toxicological assays with zero or near-to-zero proportions or counts in the concurrent negative control group

T2 - a tutorial

AU - Jaki, Thomas

AU - Kitsche, Andreas

AU - Hothorn, Ludwig A

PY - 2014

Y1 - 2014

N2 - In toxicological studies interest often lies in proportions or counts for which an increase in the dose group over control indicates a safety risk. Additionally, the control group observes values that are zero or near-to-zero for endpoints characterizing pathological processes. In such instances, the comparison of dose groups versus control requires special attention as inference for ratio-to-control is infeasible or unstable and inference for difference-to-control is highly sensitive to the number of zeros or near-to-zero values. In practice, assays are commonly performed multiple times in a laboratory so that data of some historical controls are available. When the concurrent control values fall within a corresponding normal range, the evaluation is performed by comparing doses versus the concurrent control. If the data of the concurrent control are outside the normal range, a test versus the concurrent control has either an increased risk of a false-positive result or an increased risk of a false-negative result, depending on the direction of the deviation. In this work, we discuss a simple to use Williams-type approach for comparing against a mean historical value. The idea is illustrated on three examples and we show how the method can be implemented the statistical software package R.

AB - In toxicological studies interest often lies in proportions or counts for which an increase in the dose group over control indicates a safety risk. Additionally, the control group observes values that are zero or near-to-zero for endpoints characterizing pathological processes. In such instances, the comparison of dose groups versus control requires special attention as inference for ratio-to-control is infeasible or unstable and inference for difference-to-control is highly sensitive to the number of zeros or near-to-zero values. In practice, assays are commonly performed multiple times in a laboratory so that data of some historical controls are available. When the concurrent control values fall within a corresponding normal range, the evaluation is performed by comparing doses versus the concurrent control. If the data of the concurrent control are outside the normal range, a test versus the concurrent control has either an increased risk of a false-positive result or an increased risk of a false-negative result, depending on the direction of the deviation. In this work, we discuss a simple to use Williams-type approach for comparing against a mean historical value. The idea is illustrated on three examples and we show how the method can be implemented the statistical software package R.

KW - count

KW - proportion

KW - near-to-zero

KW - historical controls

KW - poly-3 test

KW - Williams trend test

M3 - Journal article

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JO - JP Journal of Biostatistics

JF - JP Journal of Biostatistics

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