caa a22 4500 475762444 CHVBK 20180406123555.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1023/A:1009658829383 doi (NATIONALLICENCE)springer-10.1023/A:1009658829383 Litter-based methods in developmental toxicity risk assessment [Elektronische Daten] [Lieven Declerck, Geert Molenberghs, Marc Aerts, Louise Ryan] Developmental toxicity experiments are designed to assess potential adverse effects of drugs and other exposures on developing fetuses from pregnant dams. Extrapolation to humans is a very difficult problem. An important issue here is whether risk assessment should be based on the fetus or the litter level. In this paper, fetus and litter-based risks that properly account for cluster size are defined and compared for the beta-binomial model and a conditional model for clustered binary data. It is shown how the hierarchical structure of non-viable implants and viable but malformed offspring can be incorporated. Risks based on a joint model for death/resorption and malformation are contrasted with risks based on an adverse event defined as either death/resorption or malformation. The estimation of safe exposure levels for all risk types is discussed and it is shown how estimation of the cluster size distribution affects variance estimation. The methods are applied to data collected under the National Toxicology Program and in large sample simulations. Kluwer Academic Publishers, 2000 beta-binomial nationallicence clustered data nationallicence likelihood estimation nationallicence safe dose nationallicence teratology nationallicence Declerck Lieven Biostatistics, Harvard School of Public Health and Dana-Farber Cancer Institute, 02115, Boston, MA, USA aut Molenberghs Geert Biostatistics, Center for Statistics, Limburgs Universitair Centrum, B3590, Diepenbeek, Belgium aut Aerts Marc Biostatistics, Center for Statistics, Limburgs Universitair Centrum, B3590, Diepenbeek, Belgium aut Ryan Louise Biostatistics, Harvard School of Public Health and Dana-Farber Cancer Institute, 02115, Boston, MA, USA aut Environmental and Ecological Statistics Kluwer Academic Publishers 7/1(2000-03-01), 57-76 1352-8505 7:1<57 2000 7 10651 https://doi.org/10.1023/A:1009658829383 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1009658829383 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Declerck Lieven Biostatistics, Harvard School of Public Health and Dana-Farber Cancer Institute, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Molenberghs Geert Biostatistics, Center for Statistics, Limburgs Universitair Centrum, B3590, Diepenbeek, Belgium aut NATIONALLICENCE 700 1- Aerts Marc Biostatistics, Center for Statistics, Limburgs Universitair Centrum, B3590, Diepenbeek, Belgium aut NATIONALLICENCE 700 1- Ryan Louise Biostatistics, Harvard School of Public Health and Dana-Farber Cancer Institute, 02115, Boston, MA, USA aut NATIONALLICENCE 773 0- Environmental and Ecological Statistics Kluwer Academic Publishers 7/1(2000-03-01), 57-76 1352-8505 7:1<57 2000 7 10651 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer