Cover......Page 1
Half Title......Page 2
Series Page......Page 3
Title Page......Page 4
Copyright Page......Page 5
Dedication Page......Page 6
About the Series......Page 8
Preface......Page 10
Introduction......Page 12
Contents......Page 14
Unit I The LD50......Page 20
First Principles......Page 22
Introducing Uncertainty......Page 25
More Uncertainty......Page 27
Models of Sigmoid Curves......Page 30
Alternative Mathematical Models......Page 36
What Is Wrong with It All?......Page 39
Overview......Page 44
Consequences of Bliss's Formula tion......Page 46
Some Comments on Confidence Bounds on the LD 50......Page 47
Concept of a Probability Distribution......Page 52
Gaussian or Normal Distribution......Page 58
Beyond the Gaussian Distribution......Page 61
Estimating Parameters......Page 65
Finding Consistent Estimators of the LD 50......Page 68
The Spearman--Karber Solution......Page 72
Computing Confidence Bounds......Page 74
More on Confidence Bounds......Page 78
Testing Goodness of Fit......Page 79
Unit II Subchronic Toxicity Studies......Page 82
Overview......Page 84
Random Assignment of Animals to Treatment......Page 86
Observations on the Growth of Living Animals......Page 91
More Observations on Living Animals......Page 97
Statistical Tests of Hypothesis Reexamined......Page 102
Directing Statistical Tests......Page 104
Confidence Bounds on Comparisons......Page 106
Other Observations on Living Animals......Page 109
Observations Made on Organ Weights at the Time of Death......Page 110
The Overall Aim of the Study......Page 112
Well-Defined Questions......Page 116
Looking for the Car Keys......Page 117
What Is "Significant"?......Page 118
Kurskal-Wallis Nonparametric ANOVA......Page 120
Fisher's ANOV A......Page 122
Neyman-Pearson Formulation of Hypothesis Tests......Page 123
Neyman-Pearson Hypothesis Testing......Page 127
One- and Two-Sample Tests......Page 131
Analysis of Covariance......Page 134
Improper Uses of Hypothesis Tests......Page 136
Unit III Chronic Toxicity Studies......Page 140
Overview......Page 142
Comparing the Incidence of a Single Well-Defined Lesion......Page 143
Adjusting Incidence for Time on Study......Page 146
Analyzing a Single-Graded Lesion......Page 150
Comparing Multiple Lesions......Page 152
Use of Historical Controls......Page 154
Use of Count Data Only......Page 156
Asking the Right Questions......Page 157
Biology Versus Statistics......Page 160
2 x K Contingency Tables......Page 162
Adjusting for Time and Other Covariates......Page 166
Scaling Severity of Lesions......Page 168
Clustering Techniques......Page 173
Bayesian Analysis......Page 178
Measures of Risk......Page 180
Estimating Effects in a Multivariate Setting......Page 185
More on Linear Combinations......Page 190
Clustering and Directed Graphs......Page 193
References......Page 204
Index......Page 212