Continuous Model Averaging for Benchmark Dose Analysis: Averaging Over Distributional Forms.

Matthew W Wheeler, Jose Cortinas, Marc Aerts, Jeffery S Gift, J Allen Davis
Author Information
  1. Matthew W Wheeler: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, RTP, NC, USA.
  2. Jose Cortinas: European Food Safety Authority.
  3. Marc Aerts: Center for Statistics, Hasslet University.
  4. Jeffery S Gift: National Center for Environmental Assessment,US Environmental Protection Agency, RTP, NC, USA.
  5. J Allen Davis: National Center for Environmental Assessment, U.S. Environmental Protection Agency, Cincinnati, OH, USA.

Abstract

When estimating a benchmark dose (BMD) from chemical toxicity experiments, model averaging is recommended by the National Institute for Occupational Safety and Health, World Health Organization and European Food Safety Authority. Though numerous studies exist for Model Average BMD estimation using dichotomous responses, fewer studies investigate it for BMD estimation using continuous response. In this setting, model averaging a BMD poses additional problems as the assumed distribution is essential to many BMD definitions, and distributional uncertainty is underestimated when one error distribution is chosen a priori. As model averaging combines full models, there is no reason one cannot include multiple error distributions. Consequently, we define a continuous model averaging approach over distributional models and show that it is superior to single distribution model averaging. To show the superiority of the approach, we apply the method to simulated and experimental response data.

Keywords

References

  1. EFSA J. 2017 Jan 24;15(1):e04658 [PMID: 32625254]
  2. Fundam Appl Toxicol. 1984 Oct;4(5):854-71 [PMID: 6510615]
  3. J Toxicol Pathol. 2013 Mar;26(1):29-34 [PMID: 23723565]
  4. Risk Anal. 2014 Jan;34(1):101-20 [PMID: 23758102]
  5. Nucleic Acids Res. 2017 Jan 4;45(D1):D964-D971 [PMID: 27899660]
  6. Toxicol Appl Pharmacol. 2013 Nov 1;272(3):767-79 [PMID: 23954464]
  7. Environmetrics. 2012 Dec;23(8):706-716 [PMID: 23794799]
  8. Environ Health Perspect. 2018 Jan 11;126(1):017002 [PMID: 29329100]
  9. Risk Anal. 2007 Jun;27(3):659-70 [PMID: 17640214]
  10. Risk Anal. 2020 Sep;40(9):1706-1722 [PMID: 32602232]
  11. Toxicol Sci. 2002 Apr;66(2):298-312 [PMID: 11896297]
  12. Environmetrics. 2020 Nov;31(7): [PMID: 36052215]
  13. Risk Anal. 2017 Nov;37(11):2107-2118 [PMID: 28555874]
  14. Regul Toxicol Pharmacol. 2000 Aug;32(1):68-72 [PMID: 11029270]
  15. Environmetrics. 2013 May 1;24(3):143-157 [PMID: 24039461]

Grants

  1. Z99 ES999999/Intramural NIH HHS
  2. ZIA ES103357/Intramural NIH HHS
  3. ZIA ES103358/Intramural NIH HHS

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