99781449674328_FMxx.indd781449674328_FMxx.indd PagePage i 06/01/1406/01/14 8:058:05 PMPM f-w-148f-w-148 //202/JB00094/work/indd/FM202/JB00094/work/indd/FM Clinical Epidemiology Principles, Methods, and Applications for Clinical Research Diederick E. Grobbee, MD, PhD Professor of Clinical Epidemiology SECOND EDITION Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht, The Netherlands Arno W. Hoes, MD, PhD Professor of Clinical Epidemiology Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht, The Netherlands 99781449674328_FMxx.indd781449674328_FMxx.indd PagePage iiii 06/01/1406/01/14 8:058:05 PMPM f-w-148f-w-148 //202/JB00094/work/indd/FM202/JB00094/work/indd/FM World Headquarters Jones & Bartlett Learning 5 Wall Street Burlington, MA 01803 978-443-5000 [email protected] www.jblearning.com Jones & Bartlett Learning books and products are available through most bookstores and online booksellers. 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Production Credits Executive Publisher: William Brottmiller Composition: Cenveo Publisher Services Publisher: Michael Brown Cover Design: Scott Moden Associate Editor: Chloe Falivene Photo Research and Permissions Associate: Editorial Assistant: Nicholas Alakel Ashley Dos Santos Associate Production Editor: Rebekah Linga Cover Image: © Volta_ontwerpers, Utrecht Senior Marketing Manager: Sophie Fleck Teague Printing and Binding: Edwards Brothers Malloy Manufacturing and Inventory Control Supervisor: Cover Printing: Edwards Brothers Malloy Amy Bacus Library of Congress Cataloging-in-Publication Data Grobbee, D. E., author. Clinical Epidemiology: Principles, Methods, and Applications for Clinical Research / Diederick E. Grobbee and Arno W. Hoes.—Second edition. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4496-7432-8 (pbk.) ISBN 1-4496-7432-1 (pbk.) I. Hoes, Arno W., author. II. Title. [DNLM: 1. Epidemiologic Methods. 2. Epidemiologic Factors. 3. Prognosis. WA 950] RA652.2.C55 614.4—dc23 2013030779 6048 Printed in the United States of America 18 17 16 15 14 10 9 8 7 6 5 4 3 2 1 99781449674328_FMxx.indd781449674328_FMxx.indd PagePage iiiiii 06/01/1406/01/14 8:058:05 PMPM f-w-148f-w-148 //202/JB00094/work/indd/FM202/JB00094/work/indd/FM DEDICATION To Sjoukje and Carin 99781449674328_FMxx.indd781449674328_FMxx.indd PagePage iviv 06/01/1406/01/14 8:058:05 PMPM f-w-148f-w-148 //202/JB00094/work/indd/FM202/JB00094/work/indd/FM 99781449674328_FMxx.indd781449674328_FMxx.indd PagePage v 09/01/1409/01/14 12:3512:35 AMAM f-w-148f-w-148 ~~/Desktop/ramesh/Desktop/ramesh CONTENTS Preface . xi Foreword . xiii The Julius Center . xv About the Authors . xvii Contributors . xix Acknowledgments . xxi Quick Start . xxiii PART 1 OVERVIEW 1 Chapter 1: Introduction to Clinical Epidemiology 3 Introduction . 3 Clinical Epidemiology . 4 Research Relevant to Patient Care . 6 Epidemiologic Study Design . 9 Design of Data Collection . 13 Design of Data Analysis . 14 Diagnostic, Etiologic, Prognostic, and Intervention Research . 14 Moving from Research to Practice: Validity, Relevance, and Generalizability . 24 PART 2 PRINCIPLES OF CLINICAL RESEARCH 29 Chapter 2: Diagnostic Research 31 Introduction . 31 Diagnosis in Clinical Practice . 31 From Diagnosis in Clinical Practice to Diagnostic Research . 37 Diagnostic Research versus Test Research . 40 Diagnostic Research . 46 Application of Study Results in Practice . 71 Worked-Out Example . 72 v 99781449674328_FMxx.indd781449674328_FMxx.indd PagePage vivi 09/01/1409/01/14 12:3512:35 AMAM f-w-148f-w-148 ~~/Desktop/ramesh/Desktop/ramesh vi CLINICAL EPIDEMIOLOGY Chapter 3: Etiologic Research 77 Introduction . 77 Etiologic Research in Epidemiology . 78 Theoretical Design . 80 Confounding . 81 Causality . 94 Modifi cation and Interaction . 96 Modifi ers and Confounders . 105 Design of Data Collection . 107 Common Etiologic Questions in Clinical Epidemiology . 111 Worked-Out Example . 112 Chapter 4: Prognostic Research 117 Introduction . 117 Prognosis in Clinical Practice . 117 Approaches to Prognostication . 120 Prognostication Is a Multivariable Process . 122 Added Prognostic Value . 123 From Prognosis in Clinical Practice to Prognostic Research . 124 The Predictive Nature of Prognostic Research . 126 Appraisal of Prevailing Prognostic Research . 128 Prognostic Research . 131 Bias in Prognostic Research . 138 Design of Data Analysis . 138 Worked-Out Example . 143 Conclusion . 150 Chapter 5: Intervention Research: Intended Eff ects 151 Introduction . 151 Intervention Effects . 153 Treatment Effect . 163 Comparability of Natural History . 164 Randomization . 168 Comparability of Extraneous Effects . 170 Comparability of Observations . 172 99781449674328_FMxx.indd781449674328_FMxx.indd PagePage viivii 09/01/1409/01/14 12:3512:35 AMAM f-w-148f-w-148 ~~/Desktop/ramesh/Desktop/ramesh CONTENTS vii Trial Limitations . 173 The Randomized Trial as a Paradigm for Etiologic Research . 179 Chapter 6: Intervention Research: Unintended Eff ects 181 Introduction . 181 Research on Unintended Effects of Interventions . 182 Studies on Unintended Effects of Interventions: Causal Research . 185 Type A and Type B Unintended Effects . 188 Other Unintended Effects . 190 Theoretical Design . 192 Design of Data Collection . 192 Comparability in Observational Research on Unintended Effects . 201 Methods Used to Limit Confounding . 204 Healthcare Databases as a Framework for Research on Unintended Effects of Interventions . 215 PART 3 TOOLS FOR CLINICAL RESEARCH 217 Chapter 7: Design of Data Collection 219 Introduction . 219 Time . 220 Census or Sampling . 221 Experimental or Observational Studies . 224 Taxonomy of Epidemiological Data Collection . 226 Chapter 8: Cohort and Cross-Sectional Studies 229 Introduction . 229 Timing of the Association Relative to the Timing of Data Collection . 230 Causal and Descriptive Cohort Studies . 232 Experimental.