Likelihood models for clustered binary and continuous outcomes: application to developmental toxicology

Biometrics
M M Regan, P J Catalano

Abstract

In developmental toxicology, methods based on dose response modeling and quantitative risk assessment are being actively pursued. Among live fetuses, the presence of malformations and reduction in fetal weight are of primary interest, but ordinarily, the dose-response relationships are characterized in each of the outcomes separately while appropriately accounting for clustering within litters. Jointly modeling the outcomes, allowing different relationships with dose while incorporating the correlation between the fetuses and the outcomes, may be more appropriate. We propose a likelihood-based model that is an extension of a correlated probit model to incorporate continuous outcomes. Our model maintains a marginal dose-response interpretation for the individual outcomes while taking into account both the correlations between outcomes on an individual fetus and those due to clustering. The joint risk of malformation and low birth weight can then be estimated directly. This approach is particularly well suited to estimating safe dose levels as part of quantitative risk assessment.

References

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Citations

Feb 18, 2010·Journal of the American Statistical Association·Xuefeng LiuBess Marcus
Jul 1, 2014·Statistics in Medicine·Anna C SnavelyYi Li
Jan 5, 2006·Biometrical Journal. Biometrische Zeitschrift·Catalina Stefanescu, Bruce W Turnbull
Apr 2, 2010·Journal of the Royal Statistical Society. Series C, Applied Statistics·Julie S NajitaPaul J Catalano
Nov 30, 2006·Statistics in Medicine·Ying YangJie Zhang
Jul 18, 2008·Risk Analysis : an Official Publication of the Society for Risk Analysis·Zi-Fan YuPaul J Catzlano
Jul 20, 2007·Biometrical Journal. Biometrische Zeitschrift·Patrick J Farrell, Chul Gyu Park
Oct 12, 2005·Statistics in Medicine·R V Gueorguieva, G Sanacora
Dec 13, 2012·Risk Analysis : an Official Publication of the Society for Risk Analysis·Julie S Najita, Paul J Catalano
May 13, 2009·Biometrics·Lanjia LinDebajyoti Sinha
Sep 27, 2016·The Canadian Journal of Statistics = Revue Canadienne De Statistique·Esra KürümRunze Li
Dec 1, 2014·Scandinavian Journal of Statistics, Theory and Applications·Ling ZhouY I Li
Nov 21, 2014·Statistical Methods in Medical Research·Qiuju LiJohn Belcher
Sep 15, 2007·Statistical Methods in Medical Research·Charles McCulloch
Jul 3, 2018·Statistics in Medicine·Esra KürümPeter Lee

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