Deutsch Roland C, Piegorsch Walter W
Department of Mathematics & Statistics, The University of North Carolina at Greensboro, 317 College Avenue, Greensboro, NC 27402, USA.
Biom J. 2013 Sep;55(5):741-54. doi: 10.1002/bimj.201300037. Epub 2013 Jul 15.
Benchmark analysis is a widely used tool in biomedical and environmental risk assessment. Therein, estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a prespecified benchmark response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This paper demonstrates how the benchmark modeling paradigm can be expanded from the single-agent setting to joint-action, two-agent studies. Focus is on continuous response outcomes. Extending the single-exposure setting, representations of risk are based on a joint-action dose-response model involving both agents. Based on such a model, the concept of a benchmark profile-a two-dimensional analog of the single-dose BMD at which both agents achieve the specified BMR-is defined for use in quantitative risk characterization and assessment.
基准分析是生物医学和环境风险评估中广泛使用的工具。在其中，对于单一刺激的不良反应情况，诱发预先指定的基准反应（BMR）的最低暴露水平估计，即所谓的基准剂量（BMD），已得到充分理解。然而，对于同时研究两种药剂的情况，基准方法的发展还很不完善。本文展示了基准建模范式如何从单药剂设置扩展到联合作用的双药剂研究。重点是连续反应结果。扩展单暴露设置，风险表示基于涉及两种药剂的联合作用剂量反应模型。基于这样一个模型，定义了基准轮廓的概念——一种二维模拟单剂量BMD，在此两种药剂都达到指定的BMR——用于定量风险表征和评估。
