Epidemiology Kept Simple An introduction to traditional and modern epidemiology Epidemiology Kept Simple An introduction to traditional and modern epidemiology B. Burt Gerstman Department of Health Science, San Jose´ State University, San Jose,´ CA, USA, www.wiley.com/go/gerstman and www.sjsu.edu/faculty/gerstman/eks THIRD EDITION A John Wiley & Sons, Ltd., Publication This edition first published 2013, © 2013 by John Wiley & Sons, Ltd. Previous editions: 2003 by Wiley-Liss, Inc. Wiley-Blackwell is an imprint of John Wiley & Sons, formed by the merger of Wiley’s global Scientific, Technical and Medical business with Blackwell Publishing. 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Library of Congress Cataloging-in-Publication Data Gerstman, B. Burt. Epidemiology kept simple : an introduction to traditional and modern epidemiology/ B. Burt Gerstman. –3rd ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4443-3608-5 (pbk.) I. Title. [DNLM: 1. Epidemiology. 2. Epidemiologic Methods. WA 105] 614.4–dc23 2012037293 A catalogue record for this book is available from the British Library. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Cover image: iStock File #14279098. Cover design by Modern Alchemy LLC. Typeset in 9.5/12pt Meridien by Laserwords Private Limited, Chennai, India. 1 2013 To Linda Contents Preface to the Third Edition, xi Preface to the First Edition, xiii Acknowledgments, xv 1 Epidemiology Past and Present, 1 1.1 Epidemiology and its uses, 2 1.2 Evolving patterns of morbidity and mortality, 5 1.3 Selected historical figures and events, 8 1.4 Chapter summary, 30 Review questions, 31 References, 32 2 Causal Concepts, 36 2.1 Natural history of disease, 36 2.2 Variability in the expression of disease, 40 2.3 Causal models, 41 2.4 Causal inference, 48 Exercises, 58 Review questions, 61 References, 63 3 Epidemiologic Measures, 66 3.1 Measures of disease frequency, 67 3.2 Measures of association, 74 3.3 Measures of potential impact, 79 3.4 Rate adjustment, 82 Exercises, 90 Review questions, 98 References, 99 Addendum: additional mathematical details, 101 4 Descriptive Epidemiology, 104 4.1 Introduction, 104 4.2 Epidemiologic variables, 108 4.3 Ecological correlations, 116 Exercises, 121 Review questions, 123 References, 124 vii viii Contents 5 Introduction to Epidemiologic Study Design, 126 5.1 Etiologic research, 126 5.2 Ethical conduct of studies involving human subjects, 129 5.3 Selected study design elements, 130 5.4 Common types of epidemiologic studies, 137 Exercises, 138 Review questions, 140 References, 141 6 Experimental Studies, 142 6.1 Introduction, 142 6.2 Historical perspective, 144 6.3 General concepts, 146 6.4 Data analysis, 152 Exercises, 156 Review questions, 157 References, 157 7 Observational Cohort Studies, 159 7.1 Introduction, 159 7.2 Historical perspective, 161 7.3 Assembling and following a cohort, 163 7.4 Prospective, retrospective, and ambidirectional cohorts, 164 7.5 Addressing the potential for confounding, 165 7.6 Data analysis, 166 7.7 Historically important study: Wade Hampton Frost’s birth cohorts, 170 Exercises, 174 Review questions, 177 References, 177 8 Case–Control Studies, 180 8.1 Introduction, 180 8.2 Identifying cases and controls, 182 8.3 Obtaining information on exposure, 185 8.4 Data analysis, 186 8.5 Statistical justifications of case–control odds ratio as relative risks, 193 Exercises, 194 Review questions, 198 References, 199 9 Error in Epidemiologic Research, 201 9.1 Introduction, 201 9.2 Random error (imprecision), 203 9.3 Systematic error (bias), 209 Exercises, 217 Review questions, 219 References, 220 Contents ix 10 Screening for Disease, 222 10.1 Introduction, 223 10.2 Reliability (agreement), 224 10.3 Validity, 228 Summary, 238 Exercises, 239 Review questions, 243 References, 243 10.4 Chapter addendum (case study), 244 Further reading—screening for HIV, 248 Further reading—general concepts of screening, 248 Answers to case study: screening for antibodies to the human immunodeficiency virus, 249 11 The Infectious Disease Process, 255 11.1 The infectious disease process, 255 11.2 Herd immunity, 265 Exercises, 267 Review questions, 268 References, 270 12 Outbreak Investigation, 271 12.1 Background, 272 12.2 CDC prescribed investigatory steps, 273 Review questions, 282 References, 283 References—a drug–disease outbreak, 286 13 Confidence Intervals and p-Values, 302 13.1 Introduction, 303 13.2 Confidence intervals, 304 13.3 p-Values, 312 13.4 Minimum Bayes factors, 319 References, 322 14 Mantel–Haenszel Methods, 323 14.1 Ways to prevent confounding, 323 14.2 Simpson’s paradox, 325 14.3 Mantel–Haenszel methods for risk ratios, 325 14.4 Mantel–Haenszel methods for other measures of association, 329 Exercise, 335 References, 335 15 Statistical Interaction: Effect Measure Modification, 337 15.1 Two types of interaction, 337 15.2 Chi-square test for statistical, 340 15.3 Strategy for stratified analysis, 342 x Contents Exercises, 344 References, 345 16 Case Definitions and Disease Classification, 347 16.1 Case definitions, 347 16.2 International classification of disease, 351 16.3 Artifactual fluctuations in reported rates, 353 16.4 Summary, 354 References, 355 17 Survival Analysis, 356 17.1 Introduction, 356 17.2 Stratifying rates by follow-up time, 359 17.3 Actuarial method of survival analysis, 360 17.4 Kaplan–Meier method of survival analysis, 362 17.5 Comparing the survival experience of two groups, 364 Exercises, 369 References, 371 18 Current Life Tables, 373 18.1 Introduction, 373 18.2 Complete life table, 374 18.3 Abridged life table, 380 Exercises, 383 References, 384 19 Random Distribution of Cases in Time and Space, 385 19.1 Introduction, 385 19.2 The Poisson distribution, 386 19.3 Goodness of fit of the Poisson distribution, 390 19.4 Summary, 394 Exercises, 395 References, 396 Answers to Exercises and Review Questions, 398 Appendix 1: 95% Confidence Limits for Poisson Counts, 434 Appendix 2: Tail Areas in the Standard Normal (Z) Distribution: Double These Areas for Two-Sided p-Values, 436 Appendix 3: Right-Tail Areas in Chi-Square Distributions, 439 Appendix 4: Case Study—Cigarette Smoking and Lung Cancer, 441 Appendix 5: Case Study—Tampons and Toxic Shock Syndrome, 448 Index, 455 Preface to the Third Edition This major re-write of Epidemiology Kept Simple was pursued with the following objectives in mind: ● To address the American Schools of Public Health (ASPH) Epidemiology Compe- tenciesa in the first dozen chapters of the book. ● To introduce epidemiologic measures early in the book’s progression so that they can be used throughout. ● To devote full chapters to the following topics: Descriptive Epidemiology (Chapter 4), Epidemiologic Study Design (Chapter 5), Experimental Studies (Chapter 6), Observational Cohort Studies (Chapter 7), and Case–control Studies (Chapter 8). ● To provide more frequent Illustrative Examples. ● To provide additional exercises and review questions to help students learn the material. ● To extend the section on epidemiologic history (Section 1.3) to address develop- ments in the first half of the 20th century. The ASPH Epidemiology Competencies alluded to in the first bullet are: ‘‘Upon graduation a student with an MPH (Master of Public Health) should be able to: 1 Explain the importance of epidemiology for informing scientific, ethical, economic, and political discussion of health issues. 2 Describe a public health problem in terms of magnitude, person, time, and place. 3 Apply the basic terminology and definitions of epidemiology. 4 Identify key sources of data for epidemiologic purposes. 5 Calculate basic epidemiology measures. 6 Evaluate the strengths and limitations of epidemiologic reports. 7 Draw appropriate inferences from epidemiologic data. 8 Communicate epidemiologic information to lay and professional audiences. 9 Comprehend basic ethical and legal principles pertaining to the collection, main- tenance, use, and dissemination of epidemiologic data. 10 Identify the principles and limitations of public health screening programs. This list provides a framework for approaching the instruction of introductory epi- demiology to MPH students and, in my opinion, to undergraduates as well.b Most of these Competencies draw from several areas of epidemiology.