Uncertainty Modeling in Dose Response: Bench Testing Environmental Toxicity

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