Confidence Bands for Low‐Dose Risk Estimation with Quantal Response Data

We study the use of simultaneous confidence bands for low-dose risk estimation with quantal response data, and derive methods for estimating simultaneous upper confidence limits on predicted extra risk under a multistage model. By inverting the upper bands on extra risk, we obtain simultaneous lower bounds on the benchmark dose (BMD). Monte Carlo evaluations explore characteristics of the simultaneous limits under this setting, and a suite of actual data sets are used to compare existing methods for placing lower limits on the BMD.

[1]  Elaine M. Faustman,et al.  Review of noncancer risk assessment: Applications of benchmark dose methods , 1997 .

[2]  F A Smith,et al.  Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet. , 1979, Toxicology and applied pharmacology.

[3]  Walter W. Piegorsch,et al.  Exact one-sided simultaneous confidence bands via Uusipaikka’s method , 2003 .

[4]  H. Guess,et al.  Low-dose-rate extrapolation of data from animal carcinogenicity experiments— analysis of a new statistical technique , 1976 .

[5]  P. Borwein,et al.  Polynomials and Polynomial Inequalities , 1995 .

[6]  R L Kodell,et al.  Point estimates of cancer risk at low doses. , 1994, Risk analysis : an official publication of the Society for Risk Analysis.

[7]  C. Portier,et al.  Low-dose-rate extrapolation using the multistage model. , 1983, Biometrics.

[8]  Crump Ks,et al.  Confidence intervals and test of hypotheses concerning dose response relations inferred from animal carcinogenicity data. , 1977 .

[9]  K. G. Janardan.  Environmental risk assessment model for low dose extrapolation , 1995 .

[10]  Ralph L Kodell,et al.  A procedure for developing risk-based reference doses. , 2002, Regulatory toxicology and pharmacology : RTP.

[11]  H. Hotelling.  Applications of the Theory of Error to the Interpretation of Trends , 1929 .

[12]  K S Crump,et al.  A new method for determining allowable daily intakes. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[13]  C J Portier,et al.  Biostatistical issues in the design and analysis of animal carcinogenicity experiments. , 1994, Environmental health perspectives.

[14]  Kenny S. Crump,et al.  Calculation of Benchmark Doses from Continuous Data , 1995 .

[15]  A J Bailer,et al.  Estimating upper confidence limits for extra risk in quantal multistage models. , 1994, Risk analysis : an official publication of the Society for Risk Analysis.

[16]  G. Wogan,et al.  Carcinogenic effects of low dietary levels of aflatoxin B1 in rats. , 1974, Food and cosmetics toxicology.

[17]  H. Scheffé.  A METHOD FOR JUDGING ALL CONTRASTS IN THE ANALYSIS OF VARIANCE , 1953 .

[18]  V. Covello,et al.  Risk Analysis: A Guide to Principles and Methods for Analyzing Health and Environmental Risks , 1989 .

[19]  P. Armitage,et al.  The Age Distribution of Cancer and a Multi-stage Theory of Carcinogenesis , 1954, British Journal of Cancer.