Abstract
What is specific to the statistics in toxicology, and why not just use textbook statistics? The reason is the aim of regulatory toxicology: “be confident in negative results.” By toxicological studies, one would like to prove the harmlessness of new drugs. By means of the so-called proof-of-safety approach, the false-negative error rate (consumer’s risk) is directly controlled. Unfortunately, in most of the statistical textbooks and publications, the alternative proof of the efficacy of new drugs with the direct control of the false-positive error rate is used, denoted in toxicology as proof of hazard. Therefore, in this chapter, the basics of the falsification principle are presented simplistic. The commonly used proof-of-hazard approach is discussed hereinafter, focusing on testing a dose-related trend. Finally, the proof-of-safety methods for selected study types are explained by means of examples.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Bretz F, Hothorn LA (2003) Statistical analysis of monotone or non-monotone dose-response data from in vitro toxicological assays. ATLA (Alternat. Lab. Animals) 31(1):81–96
Chow S-C, Liu J-P (eds) (1998) Design and analysis of animal studies in pharmaceutical development. Marcel Dekker, New York
Denton DL, Diamond J, Zheng L (2011) Test of significant toxicity: a statistical application for assessing whether an effluent or site water is truly toxic. Environ Toxicol Chem 30(5):1117–1126
Dunnett CW (1955) A multiple comparison procedure for comparing several treatments with a control. Journal of the American Statistical Association 50(272):1096–1121
Fairweather WR, Bhattacharya A et al (1998) Biostatistical methodology in carcinogenicity studies. Drug Inf J 32:401–421
Hauschke D, Kieser M, Hothorn LA (1999) Proof of safety in toxicology based on the ratio of two means for normally distributed data. Biom J 41:295–304
Hothorn LA (2003) Statistics of interlaboratory in vitro toxicological studies. ATLA-Altern Lab Anim 31(Suppl 1):43–63
Hothorn LA, Hauschke D (2000) Identifying the maximum safe dose: a multiple testing approach. J Biopharm Stat 10:15–30
US-EPA (2013) Section 13, Test Method, Daphnid, Ceriodaphnia Dubia, survival and reproduction test. http://water.epa.gov/scitech/methods/cwa/wet/upload/2007_07_10_methods_wet_disk3_ctf13.pdf. Accessed 3 March 2013
Williams DA (1972) The comparison of several dose levels with a zero dose control. Biometrics 28(2):519–531
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Hothorn, L.A. (2014). Statistical Evaluation Methods in Toxicology. In: Reichl, FX., Schwenk, M. (eds) Regulatory Toxicology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-35374-1_44
Download citation
DOI: https://doi.org/10.1007/978-3-642-35374-1_44
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-35373-4
Online ISBN: 978-3-642-35374-1
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences