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A Simulation Study of Quantitative Risk Assessment for Bivariate Continuous Outcomes

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  • Zi‐Fan Yu
  • Paul J. Catzlano

Abstract

The neurotoxic effects of chemical agents are often investigated in controlled studies on rodents, with binary and continuous multiple endpoints routinely collected. One goal is to conduct quantitative risk assessment to determine safe dose levels. Yu and Catalano (2005) describe a method for quantitative risk assessment for bivariate continuous outcomes by extending a univariate method of percentile regression. The model is likelihood based and allows for separate dose‐response models for each outcome while accounting for the bivariate correlation. The approach to benchmark dose (BMD) estimation is analogous to that for quantal data without having to specify arbitrary cutoff values. In this article, we evaluate the behavior of the BMD relative to background rates, sample size, level of bivariate correlation, dose‐response trend, and distributional assumptions. Using simulations, we explore the effects of these factors on the resulting BMD and BMDL distributions. In addition, we illustrate our method with data from a neurotoxicity study of parathion exposure in rats.

Suggested Citation

  • Zi‐Fan Yu & Paul J. Catzlano, 2008. "A Simulation Study of Quantitative Risk Assessment for Bivariate Continuous Outcomes," Risk Analysis, John Wiley & Sons, vol. 28(5), pages 1415-1430, October.
    • Handle: RePEc:wly:riskan:v:28:y:2008:i:5:p:1415-1430
    DOI: 10.1111/j.1539-6924.2008.01082.x
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    References listed on IDEAS

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    1. Zi-Fan Yu & Paul J. Catalano, 2005. "Quantitative Risk Assessment for Multivariate Continuous Outcomes with Application to Neurotoxicology: The Bivariate Case," Biometrics, The International Biometric Society, vol. 61(3), pages 757-766, September.
    2. Meredith M. Regan & Paul J. Catalano, 1999. "Likelihood Models for Clustered Binary and Continuous Out comes: Application to Developmental Toxicology," Biometrics, The International Biometric Society, vol. 55(3), pages 760-768, September.
    3. Esben Budtz-Jørgensen & Niels Keiding & Philippe Grandjean, 2001. "Benchmark Dose Calculation from Epidemiological Data," Biometrics, The International Biometric Society, vol. 57(3), pages 698-706, September.
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