On use of the multistage dose-response model for assessing laboratory animal carcinogenicity

Daniela K. Nitcheva, Walter W Piegorsch, R. Webster West

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We explore how well a statistical multistage model describes dose-response patterns in laboratory animal carcinogenicity experiments from a large database of quantal response data. The data are collected from the US EPA's publicly available IRIS data warehouse and examined statistically to determine how often higher-order values in the multistage predictor yield significant improvements in explanatory power over lower-order values. Our results suggest that the addition of a second-order parameter to the model only improves the fit about 20% of the time, while adding even higher-order terms apparently does not contribute to the fit at all, at least with the study designs we captured in the IRIS database. Also included is an examination of statistical tests for assessing significance of higher-order terms in a multistage dose-response model. It is noted that bootstrap testing methodology appears to offer greater stability for performing the hypothesis tests than a more-common, but possibly unstable, "Wald" test.

Original languageEnglish (US)
Pages (from-to)135-147
Number of pages13
JournalRegulatory Toxicology and Pharmacology
Volume48
Issue number2
DOIs
StatePublished - Jul 2007

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Animals
Animal Models
Databases
Data warehouses
Statistical tests
Laboratory Animals
Statistical Models
Testing
Experiments

Keywords

  • Bootstrap hypothesis test
  • Cancer
  • Dose-response modeling
  • Multistage model

ASJC Scopus subject areas

  • Toxicology

Cite this

On use of the multistage dose-response model for assessing laboratory animal carcinogenicity. / Nitcheva, Daniela K.; Piegorsch, Walter W; West, R. Webster.

In: Regulatory Toxicology and Pharmacology, Vol. 48, No. 2, 07.2007, p. 135-147.

Research output: Contribution to journalArticle

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