1、 1Authors Kenneth J.Rothman Vice President Epidemiology Research,RTI Health Solutions;Professor of Epidemiology and Medicine,Boston University,Boston,Massachusetts Sander Greenland Professor of Epidemiology and Statistics University of California Los Angeles,California Timothy L.Lash Associate Profe
2、ssor of Epidemiology and Medicine Boston University,Boston,Massachusetts Contributors James W.Buehler Research Professor Department of Epidemiology,Rollins School of Public Health,Emory University,Atlanta,Georgia Jack Cahill Vice President Department of Health Studies Sector,Westat,Inc.,Rockville,Ma
3、ryland Sander Greenland Professor of Epidemiology and Statistics University of California,Los Angeles,California M.Maria Glymour Robert Wood Johnson Foundation Health and Society Scholar Department of Epidemiology,Mailman School of Public Health,Columbia University,New York,New York,Department of So
4、ciety,Human Development and Health,Harvard School of Public Health,Boston,Massachusetts Marta Gwinn Associate Director Department of Epidemiology,National Office of Public Health Genomics,Centers for Disease Control and Prevention,Atlanta,Georgia Patricia Hartge Deputy Director Department of Epidemi
5、ology and Biostatistics Program,Division of Cancer Epidemiology and Genetics,National Cancer Institute,National Institutes of Health,Rockville,Maryland Irva Hertz-Picciotto Professor Department of Public Health,University of California,Davis,Davis,California 2C.Robert Horsburgh Jr.Professor of Epide
6、miology,Biostatistics and Medicine Department Epidemiology,Boston University School of Public Health,Boston,Massachusetts Jay S.Kaufman Associate Professor Department of Epidemiology,University of North Carolina at Chapel Hill,School of Public Health,Chapel Hill,North Carolina Muin J.Khoury Director
7、 National Office of Public Health Genomics,Centers for Disease Control and Prevention,Atlanta,Georgia Timothy L.Lash Associate Professor of Epidemiology and Medicine Boston University,Boston,Massachusetts Barbara E.Mahon Assistant Professor Department of Epidemiology and Pediatrics,Boston University
8、,Novartis Vaccines and Diagnostics,Boston,Massachusetts Robert C.Millikan Professor Department of Epidemiology,University of North Carolina at Chapel Hill,School of Public Health,Chapel Hill,North Carolina Hal Morgenstern Professor and Chair Department of Epidemiology,University of Michigan School o
9、f Public Health,Ann Arbor,Michigan Jrn Olsen Professor and Chair Department of Epidemiology,UCLA School of Public Health,Los Angeles,California Keith ORourke Visiting Assistant Professor Department of Statistical Science,Duke University,Durham,North Carolina,Adjunct Professor,Department of Epidemiol
10、ogy and Community Medicine,University of Ottawa,Ottawa,Ontario,Canada Charles Poole Associate Professor Department of Epidemiology,University of North Carolina at Chapel Hill,School of Public Health,Chapel Hill,North Carolina Kenneth J.Rothman 3Vice President,Epidemiology Research RTI Health Solutio
11、ns,Professor of Epidemiology and Medicine,Boston University,Boston,Massachusetts Clarice R.Weinberg National Institute of Environmental Health Sciences,Biostatistics Branch,Research Triangle Park,North Carolina Noel S.Weiss Professor Department of Epidemiology,University of Washington,Seattle,Washin
12、gton Allen J.Wilcox Senior Investigator Epidemiology Branch,National Institute of Environmental Health Sciences/NIH,Durham,North Carolina Walter C.Willett Professor and Chair Department of Nutrition,Harvard School of Public Health,Boston,Massachusetts 4Preface and Acknowledgments This third edition
13、of Modern Epidemiology arrives more than 20 years after the first edition,which was a much smaller single-authored volume that outlined the concepts and methods of a rapidly growing discipline.The second edition,published 12 years later,was a major transition,as the book grew along with the field.It
14、 saw the addition of a second author and an expansion of topics contributed by invited experts in a range of subdisciplines.Now,with the help of a third author,this new edition encompasses a comprehensive revision of the content and the introduction of new topics that 21st century epidemiologists wi
15、ll find essential.This edition retains the basic organization of the second edition,with the book divided into four parts.Part I(Basic Concepts)now comprises five chapters rather than four,with the relocation of Chapter 5,“Concepts of Interaction,”which was Chapter 18 in the second edition.The topic
16、 of interaction rightly belongs with Basic Concepts,although a reader aiming to accrue a working understanding of epidemiologic principles could defer reading it until after Part II,“Study Design and Conduct.”We have added a new chapter on causal diagrams,which we debated putting into P art I,as it
17、does involve basic issues in the conceptualization of relations between study variables.On the other hand,this material invokes concepts that seemed more closely linked to data analysis,and assumes knowledge of study design,so we have placed it at the beginning of Part III,“Data Analysis.”Those with
18、 basic epidemiologic background could read Chapter 12 in tandem with Chapters 2 and 4 to get a thorough grounding in the concepts surrounding causal and non-causal relations among variables.Another important addition is a chapter in Part III titled,“Introduction to Bayesian Statistics,”which we hope
19、 will stimulate epidemiologists to consider and apply Bayesian methods to epidemiologic settings.The former chapter on sensitivity analysis,now entitled“Bias Analysis,”has been substantially revised and expanded to include probabilistic methods that have entered epidemiology from the fields of risk
20、and policy analysis.The rigid application of frequentist statistical interpretations to data has plagued biomedical research(and many other sciences as well).We hope that the new chapters in Part III will assist in liberating epidemiologists from the shackles of frequentist statistics,and open them
21、to more flexible,realistic,and deeper approaches to analysis and inference.As before,Part IV comprises additional topics that are more specialized than those considered in the first three parts of the book.Although field methods still have wide application in epidemiologic research,there has been a
22、surge in epidemiologic research based on existing data sources,such as registries and medical claims data.Thus,we have moved the chapter on field methods from Part II into Part IV,and we have added a chapter entitled,“Using Secondary Data.”Another addition is a chapter on social epidemiology,and cov
23、erage on molecular epidemiology has been added to the chapter on genetic epidemiology.Many of these chapters may be of interest mainly to those who are focused on a particular area,such as reproductive epidemiology or infectious disease epidemiology,which have 5distinctive methodologic concerns,alth
24、ough the issues raised are well worth considering for any epidemiologist who wishes to master the field.Topics such as ecologic studies and meta-analysis retain a broad interest that cuts across subject matter subdisciplines.Screening had its own chapter in the second edition;its content has been in
25、corporated into the revised chapter on clinical epidemiology.The scope of epidemiology has become too great for a single text to cover it all in depth.In this book,we hope to acquaint those who wish to understand the concepts and methods of epidemiology with the issues that are central to the discip
26、line,and to point the way to key references for further study.Although previous editions of the book have been used as a course text in many epidemiology teaching programs,it is not written as a text for a specific course,nor does it contain exercises or review questions as many course texts do.Some
27、 readers may find it most valuable as a reference or supplementary-reading book for use alongside shorter textbooks such as Kelsey et al.(1996),Szklo and Nieto(2000),Savitz(2001),Koepsell and Weiss(2003),or Checkoway et al.(2004).Nonetheless,there are subsets of chapters that could form the textbook
28、 material for epidemiologic methods courses.For example,a course in epidemiologic theory and methods could be based on Chapters 1,2,3,4,5,6,7,8,9,10,11 and 12 with a more abbreviated course based on Chapters 1,2,3 and 4 and 6,7,8,9,10 and 11.A short course on the foundations of epidemiologic theory
29、could be based on Chapters 1,2,3,4 and 5 and Chapter 12.Presuming a background in basic epidemiology,an introduction to epidemiologic data analysis could use Chapters 9,10,and 12,13,14,15,16,17,18 and 19,while a more advanced course detailing causal and regression analysis could be based on Chapters
30、 2,3,4 and 5,9,10,and 12,13,14,15,16,17,18,19,20 and 21.Many of the other chapters would also fit into such suggested chapter collections,depending on the program and the curriculum.Many topics are discussed in various sections of the text because they pertain to more than one aspect of the science.
31、To facilitate access to all relevant sections of the book that relate to a given topic,we have indexed the text thoroughly.We thus recommend that the index be consulted by those wishing to read our complete discussion of specific topics.We hope that this new edition provides a resource for teachers,
32、students,and practitioners of epidemiology.We have attempted to be as accurate as possible,but we recognize that any work of this scope will contain mistakes and omissions.We are grateful to readers of earlier editions who have brought such items to our attention.We intend to continue our past pract
33、ice of posting such corrections on an internet page,as well as incorporating such corrections into subsequent printings.Please consult to find the latest information on errata.We are also grateful to many colleagues who have reviewed sections of the current text and provided useful feedback.Although
34、 we cannot mention everyone who helped in that regard,we give special thanks to Onyebuchi Arah,Matthew Fox,Jamie Gradus,Jennifer Hill,Katherine Hoggatt,Marshal Joffe,Ari Lipsky,James Robins,Federico Soldani,Henrik Toft 6Srensen,Soe Soe Thwin and Tyler VanderWeele.An earlier version of Chapter 18 app
35、eared in the International Journal of Epidemiology(2006;35:765778),reproduced with permission of Oxford University Press.Finally,we thank Mary Anne Armstrong,Alan Dyer,Gary Friedman,Ulrik Gerdes,Paul Sorlie,and Katsuhiko Yano for providing unpublished information used in the examples of Chapter 33.K
36、enneth J.Rothman Sander Greenland Timothy L.Lash CONTENTS 1Introduction.1 Section-Basic Concepts 2Causation and Causal Inference.4 3Measures of Occurrence.43 4Measures of Effect and Measures of Association.68 5Concepts of Interaction.94 Section-Study Design and Conduct 6Types of Epidemiologic Studie
37、s.113 7Cohort Studies.129 8Case-Control Studies.142 9Validity in Epidemiologic Studies.162 10Precision and Statistics in Epidemiologic Studies.186 11Design Strategies to Improve Study Accuracy.210 12Causal Diagrams.227 Section-Data Analysis 13Fundamentals of Epidemiologic Data Analysis.259 14Introdu
38、ction to Categorical Statistics.288 15Introduction to Stratified Analysis.310 16Applications of Stratified Analysis Methods.339 17Analysis of Polytomous Exposures and Outcomes.362 18Introduction to Bayesian Statistics.390 19Bias Analysis.409 20Introduction to Regression Models.452 21Introduction to
39、Regression Modeling.491 Section-Special Topics 22Surveillance.535 23Using Secondary Data.561 24Field Methods in Epidemiology.574 25Ecologic Studies.596 26Social Epidemiology.620 27Infectious Disease Epidemiology.640 28Genetic and Molecular Epidemiology.660 29Nutritional Epidemiology.682 30Environmen
40、tal Epidemiology.703 31Methodologic Issues in Reproductive Epidemiology.730 32Clinical Epidemiology.756 33Meta-Analysis.768 References.806 1Chapter 1 Introduction Kenneth J.Rothman Sander Greenland Timothy L.Lash Although some excellent epidemiologic investigations were conducted before the 20th cen
41、tury,a systematized body of principles by which to design and evaluate epidemiology studies began to form only in the second half of the 20th century.These principles evolved in conjunction with an explosion of epidemiologic research,and their evolution continues today.Several large-scale epidemiolo
42、gic studies initiated in the 1940s have had far-reaching influences on health.For example,the community-intervention trials of fluoride supplementation in water that were started during the 1940s have led to widespread primary prevention of dental caries(Ast,1965).The Framingham Heart Study,initiate
43、d in 1949,is notable among several long-term follow-up studies of cardiovascular disease that have contributed importantly to understanding the causes of this enormous public health problem(Dawber et al.,1957;Kannel et al.,1961,1970;McKee et al.,1971).This remarkable study continues to produce valua
44、ble findings more than 60 years after it was begun(Kannel and Abbott,1984;Sytkowski et al.,1990;Fox et al.,2004;Elias et al.,2004;www.nhlbi.nih.gov/about/framingham).Knowledge from this and similar epidemiologic studies has helped stem the modern epidemic of cardiovascular mortality in the United St
45、ates,which peaked in the mid-1960s(Stallones,1980).The largest formal human experiment ever conducted was the Salk vaccine field trial in 1954,with several hundred thousand school children as subjects(Francis et al.,1957).This study provided the first practical basis for the prevention of paralytic
46、poliomyelitis.The same era saw the publication of many epidemiologic studies on the effects of tobacco use.These studies led eventually to the landmark report,Smoking and Health,issued by the Surgeon General(United States Department of Health,Education and Welfare,1964),the first among many reports
47、on the adverse effects of tobacco use on health issued by the Surgeon General(www.cdc.gov/Tobacco/sgr/index.htm).Since that first report,epidemiologic research has steadily attracted public attention.The news media,boosted by a rising tide of social concern about health and environmental issues,have
48、 vaulted many epidemiologic studies to prominence.Some of these studies were controversial.A few of the biggest attention-getters were studies related to Avian influenza Severe acute respiratory syndrome(SARS)Hormone replacement therapy and heart disease 2 Carbohydrate intake and health Vaccination
49、and autism Tampons and toxic-shock syndrome Bendectin and birth defects Passive smoking and health Acquired immune deficiency syndrome(AIDS)The effect of diethylstilbestrol(DES)on offspring Disagreement about basic conceptual and methodologic points led in some instances to profound differences in t
50、he interpretation of data.In 1978,a controversy erupted about whether exogenous estrogens are carcinogenic to the endometrium:Several case-control studies had reported an extremely strong association,with up to a 15-fold increase in risk(Smith et al.,1975;Ziel and Finkle,1975;Mack et al.,1976).One g
