Document Detail


Regression models and risk estimation for mixed discrete and continuous outcomes in developmental toxicology.
MedLine Citation:
PMID:  10949415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multivariate dose-response models have recently been proposed for developmental toxicity data to simultaneously model malformation incidence (a binary outcome), and reductions in fetal weight (a continuous outcome). In this and other applications, the binary outcome often represents a dichotomization of another outcome or a composite of outcomes, which facilitates analysis. For example, in Segment II developmental toxicology studies, multiple malformation types (i.e., external, visceral, skeletal) are evaluated on each fetus; malformation status may also be ordinally measured (e.g., normal, signs of variation, full malformation). A model is proposed is for fetal weight and multiple malformation variables measured on an ordinal scale, where the correlations between the outcomes and between the offspring within a litter are taken into account. Fully specifying the joint distribution of outcomes within a litter is avoided by specifying only the distribution of the multivariate outcome for each fetus and using generalized estimating equation methodology to account for correlations due to litter clustering. The correlations between the outcomes are required to characterize joint risk to the fetus, and are therefore a focus of inference. Dose-response models and their application to quantitative risk assessment are illustrated using data from a recent developmental toxicology experiment of ethylene oxide in mice.
Authors:
M M Regan; P J Catalano
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Risk analysis : an official publication of the Society for Risk Analysis     Volume:  20     ISSN:  0272-4332     ISO Abbreviation:  Risk Anal.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-09-18     Completed Date:  2000-09-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8109978     Medline TA:  Risk Anal     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  363-76     Citation Subset:  IM    
Affiliation:
Biometrics Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. meredith_regan@post.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced / etiology
Animals
Dose-Response Relationship, Drug
Female
Mice
Models, Biological
Outcome Assessment (Health Care)
Pregnancy
Regression Analysis*
Risk Assessment*
Teratogens / toxicity
Teratology / statistics & numerical data*
Grant Support
ID/Acronym/Agency:
CA09337/CA/NCI NIH HHS; ES06900/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Teratogens

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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