Veterinary Clinical Epidemiology: From Patient to Population

273 Pages·2020·6.532 MB·English

by  Ronald D. Smith

Veterinary Clinical
Epidemiology
From Patient to Population
Fourth Edition

Veterinary Clinical
Epidemiology
From Patient to Population
Fourth Edition
Ronald D. Smith
CRC Press
Taylor & Francis Group
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Contents
List of Examples ............................................................................................................................xiii
Preface to the Fourth Edition .........................................................................................................xvii
Acknowledgments ...........................................................................................................................xix
About the Cover ..............................................................................................................................xxi
Author ..........................................................................................................................................xxiii
Chapter 1 Introduction ..................................................................................................................1
1.1 Definitions .........................................................................................................1
1.2 Epidemiologic Approaches ................................................................................2
1.2.1 Quantitative Epidemiology ...................................................................2
1.2.2 Ecological Epidemiology (Medical Ecology) ......................................3
1.2.3 Etiologic Epidemiology ........................................................................3
1.2.4 Herd Health/Preventive Medicine ........................................................3
1.2.5 Clinical Epidemiology .........................................................................3
1.3 Applications of Epidemiology in Veterinary Practice.......................................4
1.4 Objectives ..........................................................................................................7
1.4.1 Development of Medical Decision-Making Skills ...............................7
1.4.2 Learn Epidemiologic Methodology and How to Analyze and
Present Data .........................................................................................9
1.4.3 Learn to Read the Medical Literature Critically ................................10
References ..................................................................................................................12
Answers to Follow-Up Questions ..............................................................................13
Chapter 2 Defining the Limits of Normality ..............................................................................15
2.1 Introduction .....................................................................................................15
2.2 Properties of Clinical Measurements ..............................................................15
2.2.1 Signs and Symptoms: Objective versus Subjective Data ...................16
2.2.2 Scales ..................................................................................................17
2.2.3 Clinical Staging ..................................................................................19
2.2.4 Validity and Reliability ......................................................................21
2.2.5 Variation .............................................................................................22
2.2.5.1 Measurement Variation .......................................................22
2.2.5.2 Biological Variation ............................................................24
2.2.5.3 How to Reduce the Effects of Variation .............................25
2.3 Distributions ....................................................................................................26
2.3.1 Basic Properties of Distributions .......................................................27
2.3.2 Shapes of Naturally Occurring Distributions.....................................28
2.3.2.1 Unimodal, Bimodal, and Multimodal ................................28
2.3.2.2 Symmetry, Skewness, and Kurtosis....................................28
2.3.2.3 Factors Influencing the Shape of Frequency Distributions ..28
2.3.3 The Normal Distribution ....................................................................31
2.4 Reference Ranges and the Criteria for Abnormality .......................................31
2.4.1 Abnormal as Unusual .........................................................................32
2.4.2 Abnormal as Associated with Disease ...............................................34
2.4.3 Abnormal as Detectable or Treatable .................................................36
v
vi Contents
References ..................................................................................................................37
Answers to Follow-Up Questions ..............................................................................37
Chapter 3 Evaluation of Diagnostic Tests ...................................................................................39
3.1 Introduction .....................................................................................................39
3.2 Test Accuracy ..................................................................................................39
3.2.1 The Standard of Validity (Gold Standard) .........................................41
3.2.2 Postmortem Examination as a Diagnostic Test ..................................41
3.3 Properties of Diagnostic Tests .........................................................................42
3.3.1 Sensitivity and Specificity (True Positive and True Negative Rates) .....43
3.3.2 False Positive and Negative Rates ......................................................45
3.3.3 Predictive Values ................................................................................45
3.3.4 The Effect of Prevalence on Predictive Values ..................................46
3.3.5 Likelihood Ratios ...............................................................................48
3.3.6 Accuracy, Reproducibility, and Concordance ....................................49
3.4 Interpretation of Tests Whose Results Fall on a Continuum ...........................49
3.4.1 Trade-Offs between Sensitivity and Specificity .................................49
3.4.2 Receiver Operating Characteristic Curve ..........................................49
3.4.3 Two-Graph Receiver Operating Characteristic Analysis ...................50
3.4.4 Selecting a Cutoff ...............................................................................51
3.5 Comparison of Diagnostic Tests ......................................................................53
3.5.1 Tests with Fixed Cutoffs .....................................................................53
3.5.2 For Test Results That Fall on a Continuum ........................................53
3.6 Sources of Bias in the Evaluation of Diagnostic Tests ....................................55
3.6.1 Relative versus True Sensitivity and Specificity ................................55
3.6.2 The Spectrum of Patients ...................................................................56
3.6.3 Bias in Associating Test Results with Disease ...................................57
3.7 Statistical Significance ....................................................................................57
References ..................................................................................................................57
Answers to Follow-Up Questions ..............................................................................58
Chapter 4 Use of Diagnostic Tests ..............................................................................................61
4.1 Introduction .....................................................................................................61
4.2 Calculation of the Probability of Disease ........................................................61
4.2.1 From a Two-by-Two Table ..................................................................61
4.2.2 Use of Bayes’ Theorem ......................................................................61
4.2.3 Use of the Likelihood Ratio to Calculate Post-Test Probabilities ......62
4.2.3.1 Conversion between the Probability of Disease and
the Odds of Disease ............................................................62
4.2.3.2 Calculation of the Post-Test Probability of Disease ............62
4.2.3.3 A Nomogram for Applying Likelihood Ratios and
Bayes’ Theorem ..................................................................63
4.2.3.4 Estimating Post-Test Probability of Disease from the
Magnitude of a Test Result .................................................64
4.2.4 Use of Post-Test Probabilities in Medical Decision-Making .............66
4.3 Multiple Tests ..................................................................................................66
4.3.1 Parallel Testing ...................................................................................66
4.3.2 Serial Testing ......................................................................................67
4.3.3 Herd Retest .........................................................................................70
4.3.4 Assumption of Independence of Multiple Test Results ......................70
Contents vii
4.4 Working with Differential Lists ......................................................................70
4.4.1 Rule-Ins and Rule-Outs: The Choice of Sensitive or Specific Tests ..70
4.5 Screening for Disease ......................................................................................71
4.5.1 Definitions ..........................................................................................71
4.5.2 Test Criteria ........................................................................................75
4.6 Increasing the Predictive Value of Diagnostic Tests .......................................75
4.7 Communication of Diagnostic Test Results ....................................................75
References ..................................................................................................................78
Answers to Follow-Up Questions ..............................................................................78
Chapter 5 Measuring the Commonness of Disease ....................................................................81
5.1 Introduction .....................................................................................................81
5.2 Expressing the Frequency of Clinical Events ..................................................81
5.2.1 Proportions, Rates, and Ratios ...........................................................81
5.2.2 Prevalence, Incidence, and Attack Rate .............................................82
5.3 Measuring the Frequency of Clinical Events ..................................................86
5.3.1 Prevalence ..........................................................................................86
5.3.2 Incidence ............................................................................................87
5.4 Factors Affecting the Interpretation of Incidence and Prevalence ..................89
5.4.1 Temporal Sequence ............................................................................89
5.4.2 Disease Duration ................................................................................90
5.4.3 Relationship among Incidence, Prevalence, and Duration of
Disease ...............................................................................................90
5.4.4 True versus Apparent Prevalence .......................................................90
5.4.5 Case Definition ...................................................................................92
5.4.6 Dangling Numerators .........................................................................92
5.4.7 Population at Risk ..............................................................................92
5.4.8 Crude versus Adjusted Rates ..............................................................93
5.5 Adjusted Rates: The Direct Method ................................................................94
5.5.1 Age-Adjusted Rates ............................................................................94
5.5.2 Rate Adjustment for Other Factors .....................................................95
5.5.3 The Choice of a Standard Population .................................................96
5.5.4 When to Adjust Rates .........................................................................96
5.5.5 The Uses of Incidence and Prevalence ...............................................96
References ..................................................................................................................97
Answers to Follow-Up Questions ..............................................................................97
Chapter 6 Risk Assessment and Prevention ................................................................................99
6.1 Risk Factors and Their Identification ..............................................................99
6.2 Factors That Interfere with the Assessment of Risk........................................99
6.3 Uses of Risk ...................................................................................................101
6.4 Comparison of Risks .....................................................................................102
6.4.1 Univariate Analysis ..........................................................................102
6.4.2 Multivariate Analysis .......................................................................102
6.4.2.1 Mantel-Haenszel Stratified Analysis ................................102
6.4.2.2 Multivariate Logistic Regression Analysis .......................103
6.5 Cohort Studies of Risk ..................................................................................103
6.5.1 True Cohort Study Designs ..............................................................103
6.5.1.1 Concurrent Cohort Studies ...............................................104
6.5.1.2 Historical Cohort Studies .................................................105
viii Contents
6.5.2 Comparing Risks in Cohort Studies .................................................106
6.5.2.1 Relative Risk .....................................................................106
6.5.2.2 Attributable Risk...............................................................107
6.5.2.3 Population Attributable Risk ............................................107
6.5.2.4 Population Attributable Fraction ......................................107
6.5.3 Limitations of Cohort Studies ..........................................................108
6.5.4 Case Series .......................................................................................109
6.6 Case-Control Studies of Risk ........................................................................110
6.6.1 Advantages of Case-Control Studies ................................................110
6.6.2 Comparing Risks in Case-Control Studies ......................................111
6.6.3 The Odds Ratio ................................................................................111
6.6.4 Bias in Case-Control Studies ...........................................................112
6.6.4.1 Bias in Selecting Groups ..................................................112
6.6.4.2 Bias in Measuring Exposure .............................................112
6.6.4.3 Presumed Temporal Relationships ...................................112
6.7 Prevalence Surveys of Risk ...........................................................................113
6.7.1 Comparing Risks in Prevalence Surveys .........................................113
6.7.2 Limitations of Prevalence Surveys ...................................................115
6.8 Biological Plausibility and Cross-Sectional Study Designs ..........................115
References ................................................................................................................116
Answers to Follow-Up Questions ............................................................................116
Chapter 7 Measuring and Communicating Prognoses .............................................................119
7.1 Expressing Prognoses ....................................................................................119
7.2 Natural History versus Clinical Course ........................................................120
7.3 Prognosis as a Rate ........................................................................................121
7.4 Survival Analysis...........................................................................................121
7.4.1 Population Models ............................................................................122
7.4.2 Cross-Sectional Studies ....................................................................124
7.4.2.1 Analysis of Longevity .......................................................124
7.4.2.2 Life Table Analysis ...........................................................125
7.4.3 Longitudinal Studies ........................................................................128
7.4.4 Interpreting Survival Curves ............................................................130
7.5 Communication of Prognoses .......................................................................130
References ................................................................................................................131
Answers to Follow-Up Questions ............................................................................131
Chapter 8 Design and Evaluation of Clinical Trials .................................................................133
8.1 Introduction ...................................................................................................133
8.2 Efficacy, Effectiveness, and Compliance ......................................................133
8.3 Clinical Trials: Structure and Evaluation ......................................................133
8.3.1 Case Definition .................................................................................135
8.3.2 Uncontrolled Clinical Trials .............................................................135
8.3.3 Comparisons across Time and Place ................................................136
8.3.4 Allocating Treatment ........................................................................138
8.3.5 Remaining in Assigned Treatment Groups ......................................138
8.3.6 Assessment of Outcome ...................................................................139
8.3.7 Placebo Effect ..................................................................................140
8.3.8 Statistical Analysis ...........................................................................140
Contents ix
8.4 Subgroups ......................................................................................................142
8.5 Clinical Trials in Practice ..............................................................................143
References ................................................................................................................143
Answers to Follow-Up Questions ............................................................................143
Chapter 9 Statistical Significance .............................................................................................145
9.1 Introduction ...................................................................................................145
9.2 Hypothesis Definition and Testing: An Overview .........................................145
9.2.1 The Steps in Hypothesis Testing: An Example ................................146
9.2.2 Results and Conclusions ...................................................................146
9.3 Interpretation of Statistical Analyses ............................................................147
9.3.1 Concluding a Difference Exists ........................................................147
9.3.1.1 The Null Hypothesis .........................................................147
9.3.1.2 Statistical Significance ......................................................148
9.3.1.3 Confidence Limits.............................................................150
9.3.1.4 Confidence Interval for a Rate or Proportion ...................150
9.3.1.5 One-Tailed versus Two-Tailed Tests of Significance ........151
9.3.2 Concluding a Difference Does Not Exist .........................................151
9.3.2.1 Statistical Significance ......................................................151
9.3.2.2 Power ................................................................................152
9.3.3 Concluding an Association Exists ....................................................152
9.3.3.1 Agreement between Tests .................................................152
9.3.3.2 Association between Two Variables .................................154
9.4 The Selection of an Appropriate Statistical Test ...........................................155
9.4.1 Censoring .........................................................................................156
9.4.2 Level of Measurement ......................................................................157
9.4.3 Number of Groups ............................................................................157
9.4.4 Nature of Groups ..............................................................................157
9.4.5 Number of Categories ......................................................................157
9.4.6 Category Size ...................................................................................157
9.4.7 Data ..................................................................................................158
9.5 Parametric and Nonparametric Tests ............................................................158
9.6 Sample Size ...................................................................................................158
9.6.1 Minimum Sample Size for Demonstrating an Extreme Outcome .....158
9.6.2 Minimum Sample Size for Estimating a Rate or Proportion
with a Specified Degree of Precision ...............................................159
9.6.3 Minimum Sample Size to Detect Differences among Groups
in Studies of Risk, Prognosis, and Treatment ..................................160
9.7 Sampling Strategies .......................................................................................160
9.7.1 Probability Sampling ........................................................................160
9.7.1.1 Simple Random Sampling ................................................160
9.7.1.2 Systematic Sampling ........................................................160
9.7.1.3 Stratified Random Sampling.............................................161
9.7.1.4 Cluster Sampling ..............................................................161
9.7.2 Nonprobability Sampling .................................................................163
9.7.2.1 Consecutive Sampling ......................................................163
9.7.2.2 Convenience Sampling .....................................................163
9.7.2.3 Judgmental Sampling .......................................................163
9.8 Multiple Comparisons ...................................................................................164