Introduction | p. 1 |
Clinical Questions and Clinical Epidemiology | p. 2 |
Health Outcomes | p. 2 |
The Scientific Basis for Clinical Medicine | p. 3 |
Basic Principles | p. 6 |
Variables | p. 6 |
Numbers and Probability | p. 6 |
Populations and Samples | p. 6 |
Bias (Systematic Error) | p. 7 |
Selection Bias | p. 7 |
Measurement Bias | p. 8 |
Confounding | p. 8 |
Chance | p. 10 |
The Effects of Bias and Chance Are Cumulative | p. 10 |
Internal and External Validity | p. 11 |
Information and Decisions | p. 12 |
Organization of this Book | p. 12 |
Frequency | p. 17 |
Are Words Suitable Substitutes for Numbers? | p. 18 |
Prevalence and Incidence | p. 18 |
Prevalence | p. 18 |
Incidence | p. 18 |
Prevalence and Incidence in Relation to Time | p. 19 |
Relationships Among Prevalence, Incidence, and Duration of Disease | p. 19 |
Some other Rates | p. 20 |
Studies of Prevalence and Incidence | p. 21 |
Prevalence Studies | p. 21 |
Incidence Studies | p. 21 |
Cumulative Incidence | p. 21 |
Incidence Density (Person-Years) | p. 22 |
Basic Elements of Frequency Studies | p. 23 |
What Is a Case? Defining the Numerator | p. 23 |
What Is the Population? Defining the Denominator | p. 25 |
Does the Study Sample Represent the Population? | p. 25 |
Distribution of Disease by Time, Place, and Person | p. 25 |
Time | p. 26 |
Place | p. 27 |
Person | p. 27 |
Uses of Prevalence Studies | p. 28 |
What Are Prevalence Studies Good For? | p. 28 |
What Are Prevalence Studies Not Particularly Good For? | p. 28 |
Abnormality | p. 31 |
Types of Data | p. 32 |
Nominal Data | p. 32 |
Ordinal Data | p. 32 |
Interval Data | p. 32 |
Performance of Measurements | p. 33 |
Validity | p. 33 |
Content Validity | p. 33 |
Criterion Validity | p. 33 |
Construct Validity | p. 34 |
Reliability | p. 34 |
Range | p. 34 |
Responsiveness | p. 34 |
Interpretability | p. 35 |
Variation | p. 35 |
Variation Resulting from Measurement | p. 35 |
Variation Resulting from Biologic Differences | p. 36 |
Total Variation | p. 37 |
Effects of Variation | p. 37 |
Distributions | p. 38 |
Describing Distributions | p. 38 |
Actual Distributions | p. 39 |
The Normal Distribution | p. 40 |
Criteria for Abnormality | p. 41 |
Abnormal = Unusual | p. 42 |
Abnormal = Associated with Disease | p. 43 |
Abnormal = Treating the Condition Leads to a Better Clinical Outcome | p. 43 |
Regression to the Mean | p. 45 |
Risk: Basic Principles | p. 50 |
Risk Factors | p. 51 |
Recognizing Risk | p. 51 |
Long Latency | p. 51 |
Immediate Versus Distant Causes | p. 51 |
Common Exposure to Risk Factors | p. 52 |
Low Incidence of Disease | p. 52 |
Small Risk | p. 52 |
Multiple Causes and Multiple Effects | p. 52 |
Risk Factors May or May Not Be Causal | p. 53 |
Predicting Risk | p. 54 |
Combining Multiple Risk Factors to Predict Risk | p. 54 |
Risk Prediction in Individual Patients and Groups | p. 54 |
Evaluating Risk Prediction Tools | p. 56 |
Calibration | p. 56 |
Discrimination | p. 56 |
Sensitivity and Specificity of a Risk Prediction Tool | p. 56 |
Risk Stratification | p. 57 |
Why Risk Prediction Tools Do Not Discriminate Well Among Individuals | p. 57 |
Clinical Uses of Risk Factors and Risk Prediction Tools | p. 58 |
Risk Factors and Pretest Probability for Diagnostic Testing | p. 58 |
Using Risk Factors to Choose Treatment | p. 58 |
Risk Stratification for Screening Programs | p. 58 |
Removing Risk Factors to Prevent Disease | p. 59 |
Risk: Exposure to Disease | p. 61 |
Studies of Risk | p. 61 |
When Experiments Are Not Possible or Ethical | p. 61 |
Cohorts | p. 62 |
Cohort Studies | p. 62 |
Prospective and Historical Cohort Studies | p. 63 |
Prospective Cohort Studies | p. 63 |
Historical Cohort Studies Using Medical Databases | p. 64 |
Case-Cohort Studies | p. 65 |
Advantages and Disadvantages of Cohort Studies | p. 65 |
Ways to Express and Compare Risk | p. 67 |
Absolute Risk | p. 67 |
Attributable Risk | p. 68 |
Relative Risk | p. 68 |
Interpreting Attributable and Relative Risk | p. 68 |
Population Risk | p. 69 |
Taking other Variables into Account | p. 71 |
Extraneous Variables | p. 71 |
Simple Descriptions of Risk | p. 71 |
Confounding | p. 71 |
Working Definition | p. 72 |
Potential Confounders | p. 72 |
Confirming Confounding | p. 72 |
Control of Confounding | p. 72 |
Randomization | p. 73 |
Restriction | p. 73 |
Matching | p. 74 |
Stratification | p. 74 |
Standardization | p. 75 |
Multivariable Adjustment | p. 75 |
Overall Strategy for Control of Confounding | p. 75 |
Observational Studies and Cause | p. 76 |
Effect Modification | p. 76 |
Risk: From Disease to Exposure | p. 80 |
Case-Control Studies | p. 81 |
Design of Case-Control Studies | p. 83 |
Selecting Cases | p. 83 |
Selecting Controls | p. 83 |
The Population Approach | p. 83 |
The Cohort Approach | p. 84 |
Hospital and Community Controls | p. 84 |
Multiple Control Groups | p. 84 |
Multiple Controls per Case | p. 85 |
Matching | p. 85 |
Measuring Exposure | p. 85 |
Multiple Exposures | p. 87 |
The Odds Ratio: An Estimate of Relative Risk | p. 87 |
Controlling for Extraneous Variables | p. 88 |
Investigation of A Disease Outbreak | p. 89 |
Prognosis | p. 93 |
Differences in Risk and Prognostic Factors | p. 93 |
The Patients Ate Different | p. 94 |
The Outcomes Are Different | p. 94 |
The Rates Are Different | p. 94 |
The Factors May be Different | p. 94 |
Clinical Course and Natural History of Disease | p. 94 |
Elements of Prognostic Studies | p. 95 |
Patient Sample | p. 95 |
Zero Time | p. 96 |
Follow-Up | p. 96 |
Outcomes of Disease | p. 96 |
Describing Prognosis | p. 97 |
A Trade-Off: Simplicity versus More Information | p. 97 |
Survival Analysis | p. 97 |
Survival of a Cohort | p. 97 |
Survival Curves | p. 98 |
Interpreting Survival Curves | p. 100 |
Identifying Prognostic Factors | p. 100 |
Case Series | p. 101 |
Clinical Prediction Rules | p. 102 |
Bias in Cohort Studies | p. 102 |
Sampling Bias | p. 103 |
Migration Bias | p. 103 |
Measurement Bias | p. 104 |
Bias from "Non-differential" Misclassification | p. 104 |
Bias, Perhaps, but does it Matter? | p. 104 |
Sensitivity Analysis | p. 104 |
Diagnosis | p. 108 |
Simplifying Data | p. 108 |
The Accuracy of a Test Result | p. 109 |
The Gold Standard | p. 109 |
Lack of Information on Negative Tests | p. 110 |
Lack of Information on Test Results in the Nondiseased | p. 110 |
Lack of Objective Standards for Disease | p. 110 |
Consequences of Imperfect Gold Standards | p. 111 |
Sensitivity and Specificity | p. 111 |
Definitions | p. 113 |
Use of Sensitive Tests | p. 113 |
Use of Specific Tests | p. 113 |
Trade-Offs between Sensitivity and Specificity | p. 113 |
The Receiver Operator Characteristic (ROC) Curve | p. 114 |
Establishing Sensitivity and Specificity | p. 115 |
Spectrum of Patients | p. 116 |
Bias | p. 116 |
Chance | p. 117 |
Predictive Value | p. 117 |
Definitions | p. 117 |
Determinants of Predictive Value | p. 118 |
Estimating Prevalence (Pretest Probability) | p. 119 |
Increasing the Pretest Probability of Disease | p. 120 |
Specifics of the Clinical Situation | p. 120 |
Selected Demographic Groups | p. 120 |
Referral Process | p. 120 |
Implications for Interpreting the Medical Literature | p. 122 |
Likelihood Ratios | p. 122 |
Odds | p. 122 |
Definitions | p. 122 |
Use of Likelihood Ratios | p. 122 |
Why Use Likelihood Ratios? | p. 123 |
Calculating Likelihood Ratios | p. 124 |
Multiple Tests | p. 125 |
Parallel Testing | p. 126 |
Clinical Prediction Rules | p. 127 |
Serial Testing | p. 128 |
Serial Likelihood Ratios | p. 128 |
Assumption of Independence | p. 129 |
Treatment | p. 132 |
Ideas and Evidence | p. 132 |
Ideas | p. 132 |
Testing Ideas | p. 133 |
Studies of Treatment Effects | p. 134 |
Observational and Experimental Studies of Treatment Effects | p. 134 |
Randomized Controlled Trials | p. 134 |
Ethics | p. 135 |
Sampling | p. 135 |
Intervention | p. 136 |
Comparison Groups | p. 138 |
Allocating Treatment | p. 139 |
Differences Arising after Randomization | p. 139 |
Patients May Not Have the Disease Being Studied | p. 140 |
Compliance | p. 140 |
Cross-over | p. 141 |
Cointerventions | p. 141 |
Blinding | p. 141 |
Assessment of Outcomes | p. 142 |
Efficacy and Effectiveness | p. 143 |
Intention-to-Treat and Explanatory Trials | p. 144 |
Superiority, Equivalence, and Non-Inferiority | p. 145 |
Variations on Basic Randomized Trials | p. 145 |
Tailoring the Results of Trials to Individual Patients | p. 146 |
Subgroups | p. 146 |
Effectiveness in Individual Patients | p. 146 |
Trials of N = 1 | p. 146 |
Alternatives to Randomized Controlled Trials | p. 147 |
Limitations of Randomized Trials | p. 147 |
Observational Studies of Interventions | p. 147 |
Clinical Databases | p. 148 |
Randomized versus Observational Studies? | p. 148 |
Phases of Clinical Trials | p. 148 |
Prevention | p. 152 |
Preventive Activities in Clinical Settings | p. 152 |
Types of Clinical Prevention | p. 152 |
Immunization | p. 153 |
Screening | p. 153 |
Behavioral Counseling (Lifestyle Changes) | p. 153 |
Chemoprevention | p. 153 |
Levels of Prevention | p. 153 |
Primary Prevention | p. 153 |
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