Biostatistics Advance Access originally published online on October 30, 2006
Biostatistics 2007 8(4):675-688; doi:10.1093/biostatistics/kxl037
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Estimation of the benchmark dose by structural equation models
Department of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, entrance B, PO Box 2099, DK-1014 Copenhagen K, Denmark and Institute of Public Health, University of Southern Denmark, Winslowparken 17, DK-5000 Odense C, Denmark ebj{at}biostat.ku.dk
While epidemiological data typically contain a multivariate response and often also multiple exposure parameters, current methods for safe dose calculations, including the widely used benchmark approach, rely on standard regression techniques. In practice, dose–response modeling and calculation of the exposure limit are often based on the seemingly most sensitive outcome. However, this procedure ignores other available data, is inefficient, and fails to account for multiple testing. Instead, risk assessment could be based on structural equation models, which can accommodate both a multivariate exposure and a multivariate response function. Furthermore, such models will allow for measurement error in the observed variables, which is a requirement for unbiased estimation of the benchmark dose. This methodology is illustrated with the data on neurobehavioral effects in children prenatally exposed to methylmercury, where results based on standard regression models cause an underestimation of the true risk.
Keywords: Environmental epidemiology; Measurement error; Multiple endpoints; Risk assessment
Received October 11, 2005; revised June 23, 2006; revised September 12, 2006; revised October 13, 2006; accepted for publication October 20, 2006.