A shared response model for clustered binary data in developmental toxicity studies

Zhen Pang, Anthony Y.C. Kuk

Research output: Journal article publicationJournal articleAcademic researchpeer-review

7 Citations (Scopus)

Abstract

Existing distributions for modeling fetal response data in developmental toxicology such as the beta-binomial distribution have a tendency of inflating the probability of no malformed fetuses, and hence understating the risk of having at least one malformed fetus within a litter. As opposed to a shared probability extra-binomial model, we advocate a shared response model that allows a random number of fetuses within the same litter to share a common response. An explicit formula is given for the probability function and graphical plots suggest that it does not suffer from the problem of assigning too much probability to the event of no malformed fetuses. The EM algorithm can be used to estimate the model parameters. Results of a simulation study show that the EM estimates are nearly unbiased and the associated confidence intervals based on the usual standard error estimates have coverage close to the nominal level. Simulation results also suggest that the shared response model estimates of the marginal malformation probabilities are robust to misspecification of the distributional form, but not so for the estimates of intralitter correlation and the litter-level probability of having at least one malformed fetus. The proposed model is fitted to a set of data from the U.S. National Toxicology Program. For the same dose-response relationship, the fit based on the shared response distribution is superior to that based on the beta-binomial, and comparable to that based on the recently proposed q-power distribution (Kuk, 2004, Applied Statistics53, 369-386). An advantage of the shared response model over the q-power distribution is that it is more interpretable and can be extended more easily to the multivariate case. To illustrate this, a bivariate shared response model is fitted to fetal response data involving visceral and skeletal malformation.
Original languageEnglish
Pages (from-to)1076-1084
Number of pages9
JournalBiometrics
Volume61
Issue number4
DOIs
Publication statusPublished - 1 Dec 2005
Externally publishedYes

Keywords

  • Developmental toxicity data
  • Dose-response function
  • EM algorithm
  • Exchangeability
  • Intracluster correlation
  • Odds ratio
  • Risk assessment

ASJC Scopus subject areas

  • Statistics and Probability
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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