Carcinogenicity: The Design, Analysis, and Interpretation of Long-Term Animal Studies

Front Matter....Pages i-xvi
Front Matter....Pages xix-xix
Assumptions in Analyses of the Bioassay: a Statistician’s View....Pages 1-10
Biological Assumptions in Analysis of the Bioassay....Pages 11-20
Biological Assumptions in the Bioassay....Pages 21-22
Front Matter....Pages N1-N1
Statistical Tests with Historical Controls....Pages 23-38
The Value of Historical Control Data....Pages 39-51
Value of Historical Control Data....Pages 53-54
Front Matter....Pages N3-N3
Integration of Pharmacokinetics and Pathological Data in Dose Selection for Chronic Bioassays....Pages 55-64
Cancer Risk Assessment for Pharmaceutical Agents: Modifications of Laboratory Assays for Tumorigenic Activity....Pages 65-72
Dose Selection....Pages 73-74
Front Matter....Pages N5-N5
Criteria for Classification of Neoplasms for Pathologists and Statisticians....Pages 75-82
Weight-of-Biological Evidence Approach for Assessing Carcinogenicity....Pages 83-95
Statistical Considerations in the Evaluation of Graded Responses in Carcinogenesis Studies....Pages 97-105
Criteria for Classifying Neoplasms and Use of Data on Nonneoplastic Lesions....Pages 107-107
Front Matter....Pages N7-N7
Factors Affecting Histopathologic Interpretation of Toxicity—Carcinogenicity Studies....Pages 109-118
Consistency of Pathologist’s Diagnoses in the ED 01 Experiment....Pages 119-132
Society of Toxicologic Pathologists Position Paper: “Blinded” Microscopic Examination of Tissues from Toxicologic or Oncogenic Studies....Pages 133-135
Observer Bias in Histopathological Examinations....Pages 137-147
Front Matter....Pages N9-N9
Modulating Factors: Challenges to Experimental Design....Pages 149-172
Experimental Design Determines Outcome Interpretation to a Large Extent: Examples from Two-Stage Carcinogenesis Protocols....Pages 173-179
Modulating Factors: Challenges to Experimental Design....Pages 181-181
Front Matter....Pages N11-N11
Guidelines for Combining Neoplasms for Evaluation of Rodent Carcinogenesis Studies....Pages 183-196
The Aggregation of Incidence Data in Carcinogenesis Assays....Pages 197-205
Front Matter....Pages N13-N13
Reevaluation of Pathology Data in the Regulatory Decision Process....Pages 207-215
Options for Aggregation of Incidence Data and Reevaluation of Pathology Data in Regulatory Decision Process....Pages 217-219
Front Matter....Pages N15-N15
Combining Evidence from Multiple Studies....Pages 221-226
Interpretation of Multiple Studies and Design of Repeat Studies....Pages 227-237
Interpretation of Multiple Studies and Design of Repeat Studies....Pages 239-239
Front Matter....Pages N17-N17
Issues in Decision Making....Pages 241-269
Back Matter....Pages 271-279