Uncertainty Modeling in Dose Response (eBook)

ROGER M. COOKE, PhD, is Professor in the Department of Mathematics at Delft University of Technology, the Netherlands, and Chauncey Starr Senior Fellow for Risk Analysis at Resources for the Future, a nonprofit organization based in Washington, D.C., that conducts independent research on environmental, energy, and natural resource issues. Recognized as one of the world's leading authorities on mathematical modeling of risk and uncertainty, Dr. Cooke's research has widely influenced risk assessment methodology, particularly in the areas of expert judgment and uncertainty analysis.

Acknowledgments ix

Contributors xi

Introduction 1
Roger M. Cooke and Margaret MacDonell

1 Analysis of Dose-Response Uncertainty Using Benchmark Dose Modeling 17
Jeff Swartout

Comment: The Math/Stats Perspective on Chapter 1: Hard Problems Remain 34
Allan H. Marcus

Comment: EPI/TOX Perspective on Chapter 1: Re-formulating the Issues 37
Jouni T. Tuomisto

Comment: Regulatory/Risk Perspective on Chapter 1: A Good Baseline 42
Weihsueh Chiu

Comment: A Question Dangles 44
David Bussard

Comment: Statistical Test for Statistics-as-Usual Confi dence Bands 45
Roger M. Cooke

Response to Comments 47
Jeff Swartout

2 Uncertainty Quantifi cation for Dose-Response Models Using Probabilistic Inversion with Isotonic Regression: Bench Test Results 51
Roger M. Cooke

Comment: Math/Stats Perspective on Chapter 2: Agreement and Disagreement 82
Thomas A. Louis

Comment: EPI/TOX Perspective on Chapter 2: What Data Sets Per se Say 87
Lorenz Rhomberg

Comment: Regulatory/Risk Perspective on Chapter 2: Substantial Advances Nourish Hope for Clarity? 97
Rob Goble

Comment: A Weakness in the Approach? 105
Jouni T. Tuomisto

Response to Comments 107
Roger Cooke

3 Uncertainty Modeling in Dose Response Using Nonparametric Bayes: Bench Test Results 111
Lidia Burzala and Thomas A. Mazzuchi

Comment: Math/Stats Perspective on Chapter 3: Nonparametric Bayes 147
Roger M. Cooke

Comment: EPI/TOX View on Nonparametric Bayes: Dosing Precision 150
Chao W. Chen

Comment: Regulator/Risk Perspective on Chapter 3: Failure to Communicate 153
Dale Hattis

Response to Comments 160
Lidia Burzala

4 Quantifying Dose-Response Uncertainty Using Bayesian Model Averaging 165
Melissa Whitney and Louise Ryan

Comment: Math/Stats Perspective on Chapter 4: Bayesian Model Averaging 180
Michael Messner

Comment: EPI/TOX Perspective on Chapter 4: Use of Bayesian Model Averaging for Addressing Uncertainties in Cancer Dose-Response Modeling 183
Margaret Chu

Comment: Regulatorary/Risk Perspective on Chapter 4: Model Averages, Model Amalgams, and Model Choice 185
Adam M. Finkel

Response to Comments 194
Melissa Whitney and Louise Ryan

5 Combining Risks from Several Tumors Using Markov Chain Monte Carlo 197
Leonid Kopylev, John Fox, and Chao Chen

6 Uncertainty in Dose Response from the Perspective of Microbial Risk 207
P. F. M. Teunis

7 Conclusions 217
David Bussard, Peter Preuss, and Paul White

Author Index 225

Subject Index 229