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Risk Anal ; 37(4): 716-732, 2017 04.
Article in English | MEDLINE | ID: mdl-27322778

ABSTRACT

This article describes several approaches for estimating the benchmark dose (BMD) in a risk assessment study with quantal dose-response data and when there are competing model classes for the dose-response function. Strategies involving a two-step approach, a model-averaging approach, a focused-inference approach, and a nonparametric approach based on a PAVA-based estimator of the dose-response function are described and compared. Attention is raised to the perils involved in data "double-dipping" and the need to adjust for the model-selection stage in the estimation procedure. Simulation results are presented comparing the performance of five model selectors and eight BMD estimators. An illustration using a real quantal-response data set from a carcinogenecity study is provided.


Subject(s)
Dose-Response Relationship, Drug , Risk Assessment/methods , Carcinogens , Computer Simulation , Humans , Models, Statistical , No-Observed-Adverse-Effect Level , Regression Analysis
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