Lilienfeld’s Foundations of Epidemiology Lilienfeld’s Foundations Fourth Edition of Epidemiology Dona SchneiDer, Ph.D., M.P.h., F.a.c.e. DaviD e. LiLienFeLD , M.D., M.S. enGin., M.P.h., F.a.c.e. Original Edition by abrahaM M. LiLienFeLD , M.D., M.P.h., D.Sc. (hon.), F.a.c.e. 3 1 Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offices in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Oxford is a registered trademark of Oxford University Press in the UK and certain other countries. Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016 © Oxford University Press 2015 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by license, or under terms agreed with the appropriate reproduction rights organization. Inquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above. You must not circulate this work in any other form and you must impose this same condition on any acquirer. Library of Congress Cataloging-in-Publication Data Foundations of epidemiology. Lilienfeld’s foundations of epidemiology / Dona Schneider, David E. Lilienfeld; original edition by Abraham M. Lilienfeld. — Fourth edition. p. ; cm. Preceded by Foundations of epidemiology / revised by David E. Lilienfeld, Paul D. Stolley. 3rd ed. 1994. Includes bibliographical references and index. ISBN 978–0–19–537767–5 I. Schneider, Dona, 1946–. II. Lilienfeld, David E. 1957–. III. Title. [DNLM: 1. Epidemiologic Methods. 2. Epidemiology. WA 950] RA651 614.4—dc23 2015006834 9 8 7 6 5 4 3 2 1 Printed in the United States of America on acid-free paper Abraham Morris Lilienfeld (1920–1984), University Distinguished Service Professor at the Johns Hopkins University School of Hygiene and Public Health, wrote the first edition of this book in 1975/6. That edition reflected Lilienfeld’s lifelong focus on teaching. One former student described him as having been born “with a piece of chalk in his hand,” and with that chalk he would paint rainbows of epidemiology across the blackboard. Students always had priority in scheduling meetings with Lilienfeld. When those meetings came at the end of the day, he would, at the last minute, regu- larly invite students home to continue the discussion over dinner. A black- board hung in the family’s kitchen to the side of the informal dining table for precisely this purpose. Doctoral students also sat at that table to review their thesis work with him, or, if more space was required, at the bigger table in the dining room. Lilienfeld went to great lengths to teach and advocate for epidemiology in any and all venues. He was one of the founders of the University of Minnesota at Minneapolis Summer Program, where he taught epidemiology for three weeks each year. When Alexander Langmuir, his mentor, left Johns Hopkins to found the Epidemic Intelligence Service (EIS) at the Centers for Disease Control, he called upon Lilienfeld to teach introductory epidemiology to all EIS officers during the program’s early years. When asked at the last min- ute to entertain a prominent Kenyan government economics official for the university president, Lilienfeld brought the guest home to “meet the family.” During the evening, he regaled the visitor with tales about John Snow and the cholera outbreak investigations. He brought out and showed his guest a piece of the wooden water pipe involved in the outbreak that he husbanded that year as President of the American Epidemiological Society. A few years later, when the Kenyan official’s son came to the United States after receiving his MD degree, he attended Johns Hopkins to study epidemiology. Lilienfeld organized the Public Health Option in the pre-baccalaureate pro- gram at Johns Hopkins during the early 1970s, volunteering to teach an introductory epidemiology class for seniors. When the American Journal of Epidemiology was struggling financially in the late 1960s, Lilienfeld suggested that the Society for Epidemiological Research (SER) might be interested in sponsoring the journal. The society subsequently did so. Lilienfeld took great pride in how many SER members learned about different aspects of epide- miology in the course of reading the journal. And, when the first edition of this text appeared, this consummate teacher insisted on keeping the price of the book as low as possible to facilitate access by all students, from under- graduates to post-doctoral fellows. The book appeared at a price of $19.95. Abraham M. Lilienfeld embodied devotion to teaching about epidemiology to all who would listen. It is to his memory that we dedicate this book, in the spirit of introductory epidemiology as the cornerstone of public health and medicine. CONTENTS Foreword ix Preface xiii PART I | Introduction to Epidemiology 1 1 Laying the Foundations  3 2 Threads of Epidemiologic History  21 3 Selected Epidemiologic Concepts  39 4 Inferring Causal Relationships  59 PART II | Descriptive Studies 71 5 Vital Statistics  73 6 Using Vital Statistics  101 7 Morbidity Statistics  119 8 Using Morbidity Statistics  151 PART III | Analytic Studies 167 9 Observational Studies: Cohort Studies  169 10 Observational Studies: Case-Control Studies  193 11 Experimental Studies: Randomized Controlled Trials  213 12 Experimental Studies: Community and Cluster Randomized Trials  233 PART IV | Using Epidemiologic Information 249 13 Clinical Applications  251 14 Field Epidemiology  267 15 Evidence-Based Practices  285 PART V | Conclusion 297 Appendices 1 Guide to Reading the Epidemiologic Literature  299 2 Standards for Reporting the Results of Epidemiologic and Health-Related Studies  301 3 Answers to Problem Sets  303 Index  315 | viii contEnts FOREWORD The first edition of this text appeared in 1976, but, as explained to me on multiple occasions by the author (my father), its origins trace to more than two decades before. Abraham Morris Lilienfeld trained as an epidemi- ologist with a focus on infectious diseases. On completion of his training, he joined the epidemiology faculty at the Johns Hopkins School of Hygiene and Public Health (JHU), where he became interested in liver cirrhosis fol- lowing his work on an infectious hepatitis outbreak in the early 1950s. The etiology of liver cirrhosis was not well understood at that time, but the preva- lent hypothesis attributed the disease to alcoholism—not to an infectious agent. Lilienfeld examined the alcohol–liver cirrhosis relationship using the only epidemiologic methods he had available—those traditionally used to examine the etiology of infectious diseases. The utility of those methods for studying noninfectious diseases quickly became evident to him. When Lilienfeld assumed leadership of the epidemiology program at Roswell Park Memorial Cancer Institute in Buffalo, New York, in 1953, he brought with him a plan to apply traditional epidemiologic methods to study the etiology of cancer. He conceptualized the issue of breast cancer mortal- ity in a new way, with susceptibility to the disease varying with menopausal status, similar to the way susceptibility to an infectious agent varies based on immunization status. This change in framing the question allowed him to demonstrate the benefit of using traditional epidemiologic tools with the emerging diseases of the time—heart disease, cancer, and stroke. Lilienfeld returned to JHU with a reputation as a methodological innova- tor. In 1965 the World Health Organization Cancer Unit asked him to col- laborate on a book for health care professionals on epidemiologic methods