You are on page 1of 283
THIRD EDITION Clinical Epidemiology THE ESSENTIALS Robert H. Fletcher, M.D., M.Sc. Professor Department of Ambulatory Care and Prevention Hervard Medical School and Harvard Community Health Plan Department of Epidemiology, Flarvard School of Publie Health Department of Medicine, Brigham aud Women’s Hospital Boston, Massachusetts Suzanne W. Fletcher, M.D., M.Sc. Professor Department of Ambulatory Care and Prevention Harvard Medical School and Harvard Community Health Plan Department of Epidemiology, Harvard School of Public Health Department of Medicine, Brigham and Women’s Flospital Boston, Massachusetts Edward H. Wagner, M.D., M.P.H. Director, Center for Health Studies Croup Health Cooperative of Puget Sound Professor of Health Services University of Washington Seattle, Washington Ry Cosmas uonSAgs aS ML eH SERY Tasos KHOA Editur: Terovy 8, Satterisid Manages Ezttor: Crysiat Taylor Productiin: Coudreter. Raymond E, Reter Copy Eaitor: Candace B. Levy, Ph.D. Designer: Norman W. Cich fusiraten Plaroer Mor Fomandez Typesetter: Tapaco, Ino., Akron, Penneyivanea Pantor & Binder Victor Graphics, In., Baltimore, Maryland Copyright © 1996 Willers & W/kins 351 West Camden Street Ballinore, Mergandl 21201-2496 USA Rose Tres Corporate Cantor 1400 North Providence Read Builting I Suite 5025 Media, Panneylvanis 15063 2043 USA Allrights raseved. This book is protected by copzight No part of this book may be reproduced in ‘any form or by any means, inelucing photocopying. or utiized by any formation storage and retioval system without written pentission trom the copyright owner Accurate hedicalions, adverse reactions and dosage schedues for drugs are provid in this book, but itis possitle that they may change. The reader is urgoc! to review Ihe package information dat of the manufacturers of the medications mentioned Printod in the United States of America Fiet Fetion, 982 Second Eatlion, 1988 Library of Congress Cataloging-in-Publication Data Fletcher, Fotert H. Glinical epidemiotagy: the essentiale/Robat H. Flotoner. ‘Suzanne WY. Fletcher, Eaward H. Wager. -- Src 2c. pb. om Includes biblographical references and index. ISBN 0.623-09260-0 +. Clnigal epidemiology. |. Wanner, Edward H. (Edvard Haris), 1940- I tle, TDNIM: |. Epidemiologic Methods, WA 950 F514 1996] RABS2.2.C86Fo7 1996 B14.4—de70 BNI MOLG for Lirary of Congress 30-8982 ap The publishers have made every eff to ace the copyright! Rofdsrs for borrowed! mated f they have inadvertenily overtooked ary, Ihey vel be pleased to make the nevessasy arrangement: at the frst opportunity, 96 96 97 98 93 12945678910 PREFACE Since the Second Edition was written in 1988, the pace of change in medicine has accelerated. Changes have brought greater recognition of the perspectives and methods of clinical epidemiology. Countries throughout the world have, in their efforts to provide high- quality health care, experienced growing difficulties controlling the cost of care. The tension between demands for care and resources to provide it have inercased the need for better information about clinical effectiveness in setting priorities. It has become clearer that not all clinical care is effective and that the outcomes of care are the best way of judging effectiveness. Variations in care among clinicians and regions, not expiained by patients’ needs and not accompanied by similar differences in outcomes, have raised questions about which practices are best. All these forces in modern suciety have increased the value of good clinical research and of those who can perform and interpret this research properly. Phenomenal advances in understanding, the biology of disease, cspe- cially at the molecular levei, have also occurred. Discoveries in the labora- tory increase the need for good patient-based research. They must be tested in patients before they can be accepted as clinically useful. Thus the wo— laboratory science and clinical epidemiology —complement each other and are not alternatives or competitors. Other aspects of medicine are timeless. Patients and physicians still face the same kinds of questions about diagnosis, prognosis, and treatment and still value the same outcomes: to relieve suffering, restore function, and prevent untimely death. We rely on the same basic strategies (cohort and case-control studies, randomized trials, and the like) to answer the ques- tions. The inherent uncertainty of all clinical information, even that based on the best studies, persists. In preparing the third edition of this text, we have tried to take into account the sweeping, changes in medicine as well as what has not changed. We have left the basic structure of the book intact. We updated examples throughout in recognition that some diseases, such as ATDS, are new and others, such as peptic ulcer disease, are better understood. We have tried to remember that the book’s niche is as an introduction v