Clinical Epidemiology: The Essentials

274 Pages·2012·5.62 MB·English

by  Robert H. Fletcher MD MSc

Clinical
Epidemiology
The Essentials

Clinical
Epidemiology
The Essentials
Fifth Edition
Robert H. Fletcher, MD, MSc
Professor Emeritus
Department of Population Medicine
Harvard Medical School
Boston, Massachusetts
Adjunct Professor
Departments of Epidemiology and Social Medicine
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
Suzanne W. Fletcher, MD, MSc
Professor Emerita
Department of Population Medicine
Harvard Medical School
Boston, Massachusetts
Adjunct Professor
Departments of Epidemiology and Social Medicine
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina
Grant S. Fletcher, MD, MPH
Assistant Professor of Medicine
The University of Washington School of Medicine
Seattle, Washington
Acquisitions Editor: Susan Rhyner
Product Manager: Catherine Noonan
Marketing Manager: Joy Fisher-Williams
Designer: Teresa Mallon
Compositor: Aptara, Inc.
Fifth Edition
Copyright © 2014, 2005, 1996, 1988, 1982 Lippincott Williams & Wilkins, a Wolters Kluwer business.
351 West Camden Street Two Commerce Square
Baltimore, MD 21201 2001 Market Street
Philadelphia, PA 19103
Printed in China
All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted
in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized
by any information storage and retrieval system without written permission from the copyright owner, except
for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by
individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned
copyright. To request permission, please contact Lippincott Williams & Wilkins at 2001 Market Street,
Philadelphia, PA 19103, via email at [email protected], or via website at lww.com (products and services).
9 8 7 6 5 4 3 2 1
Library of Congress Cataloging-in-Publication Data
Fletcher, Robert H.
Clinical epidemiology : the essentials / Robert H. Fletcher, Suzanne
W. Fletcher, Grant S. Fletcher. – 5th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4511-4447-5 (alk. paper)
I. Fletcher, Suzanne W. II. Fletcher, Grant S. III. Title.
[DNLM: 1. Epidemiologic Methods. WA 950]

614.4–dc23
2012022346
DISCLAIMER
Care has been taken to confirm the accuracy of the information present and to describe generally accepted
practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any
consequences from application of the information in this book and make no warranty, expressed or implied,
with respect to the currency, completeness, or accuracy of the contents of the publication. Application of this
information in a particular situation remains the professional responsibility of the practitioner; the clinical
treatments described and recommended may not be considered absolute and universal recommendations.
The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set
forth in this text are in accordance with the current recommendations and practice at the time of publication.
However, in view of ongoing research, changes in government regulations, and the constant flow of information
relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any
change in indications and dosage and for added warnings and precautions. This is particularly important when
the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA)
clearance for limited use in restricted research settings. It is the responsibility of the health care provider to
ascertain the FDA status of each drug or device planned for use in their clinical practice.
To purchase additional copies of this book, call our customer service department at [phone] or fax orders
to [phone]. International customers should call [phone].
Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkins
customer service representatives are available from 8:30 am to 6:00 pm, EST.
P r e f a c e
This book is for clinicians—physicians, nurses, physi- necessary to make them suitable. Local “journal
cians’ assistants, psychologists, veterinarians, and oth- clubs” now carefully evaluate pivotal articles rather
ers who care for patients—who want to understand than survey the contents of several journals. The
for themselves the strength of the information base National Library of Medicine now includes search
for their clinical decisions. Students of epidemiology terms in MEDLINE for research methods, such as
and public health may also find this book useful as a randomized controlled trial and meta-analysis. In
complement to the many excellent textbooks about short, clinical medicine and epidemiology are mak-
epidemiology itself. ing common cause. “Healing the schism” is what
To reach full potential, modern clinicians should Kerr White called it.
have a basic understanding of clinical epidemiology Third, the care of patients should be fun. It is not
for many reasons. fun to simply follow everyone else’s advice without
First, clinicians make countless patient care deci- really knowing what stands behind it. It is exhaust-
sions every day, some with very high stakes. It is their ing to work through a vast medical literature, or
responsibility to base those decisions on the best even a few weekly journals, without a way of quickly
available evidence, a difficult task because the evi- deciding which articles are scientifically strong and
dence base is vast and continually changing. At the clinically relevant and which are not worth bothering
simplest level, responsible care can be accomplished with. It is unnerving to make high-stakes decisions
by following carefully prepared recommendations without really knowing why they are the right ones.
found in evidence-based guidelines, review articles, or To capture all the enjoyment of their profession, cli-
textbooks, but patient care at its best is far more than nicians need to be confident in their ability to think
that. Otherwise, it would be sufficient to have it done about evidence for themselves, even if someone else
by technicians following protocols. Sometimes the has done the heavy lifting to find and sort that evi-
evidence is contradictory, resulting in “toss-up” deci- dence, by topic and quality, beforehand. It is fun to
sions. The evidence may be weak, but a decision still be able to confidently participate in discussions of
needs to be made. Recommendations that are right clinical evidence regardless of whether it is within
for patients on average need to be tailored to the spe- one’s specialty (as all of us are nonspecialists in every-
cific illnesses, behaviors, and preferences of individual thing outside our specialty).
patients. Expert consultants may disagree, leaving the In this book, we have illustrated concepts with
clinicians with primary responsibility for the patient examples from patient care and clinical research,
in the middle. Special interests—by for-profit compa- rather than use hypothetical examples, because medi-
nies or clinicians whose income or prestige is related cine is so deeply grounded in practical decisions about
to their advice—may affect how evidence is summa- actual patients. The important questions and studies
rized. For these reasons, clinicians need to be able have evolved rapidly and we have updated examples
to weigh evidence themselves in order to meet their to reflect this change, while keeping examples that
responsibilities as health care professionals. represent timeless aspects in the care of patients and
Second, clinical epidemiology is now a central classic studies.
part of efforts to improve the effectiveness of patient As clinical epidemiology becomes firmly estab-
care worldwide. Clinicians committed to research lished within medicine, readers expect more from an
careers are pursuing formal postgraduate training in entry-level textbook. We have, therefore, added new
research methods, often in departments of epidemi- topics to this edition. Among them are comparative
ology. Grants for clinical research are judged largely effectiveness, practical clinical trials, noninferiority
by the principles described in this book. Clinical trials, patient-level meta-analyses, and modern con-
epidemiology is the language of journal peer review cepts in grading evidence-based recommendations.
and the “hanging committees” that decide whether We have also discussed risk, confounding, and effect
research reports should be published and the revisions modification in greater depth.
v
vi Preface
Modern research design and analyses, supported Clinical epidemiology is now considered a cen-
by powerful computers, make it possible to answer tral part of a broader movement, evidence-based
clinical questions with a level of validity and gen- medicine. This is in recognition of the importance, in
eralizability not dreamed of just a few years ago. addition to judging the validity and generalizability
However, this often comes at the cost of complexity, of clinical research results, of asking questions that
placing readers at a distance from the actual data and can be answered by research, finding the available evi-
their meaning. Many of us may be confused as highly dence, and using the best of that evidence in the care
specialized research scientists debate alternative of patients. We have always considered these addi-
meanings of specific terms or tout new approaches to tional competencies important, and we give them
study design and statistical analyses, some of which even more attention in this edition of the book.
seem uncomfortably like black boxes no matter how We hope that readers will experience as much
hard we try to get inside them. In such situations, it enjoyment and understanding in the course of read-
is especially valuable to remain grounded in the basics ing this book as we have in writing it.
of clinical research. We have tried to do just that with
the understanding that readers may well want to go Robert H. Fletcher
on to learn more about this field than is possible from Suzanne W. Fletcher
an introductory textbook alone. Grant S. Fletcher
A c k n o w l e d g m e n t s
We are fortunate to have learned clinical epidemi- people and now learns from medical students, resi-
ology from its founders. Kerr White was Bob and dents, and faculty colleagues as he teaches them about
Suzanne’s mentor during postgraduate studies at the care for patients at Harborview Hospital and the
Johns Hopkins and convinced us that what matter University of Washington.
are “the benefits of medical interventions in relation While editors of the Journal of General Inter-
to their hazards and costs.” Alvan Feinstein taught nal Medicine and Annals of Internal Medicine, Bob
a generation of young clinician–scholars about the and Suzanne learned from fellow editors, including
“architecture of clinical research” and the dignity of members of the World Association of Medical Edi-
clinical scholarship. Archie Cochrane spent a night tors (WAME), how to make reports of research more
at our home in Montreal when Grant was a boy and complete, clear, and balanced so that readers can
opened our eyes to “effectiveness and efficiency.” understand the message with the least effort. With
David Sackett asserted that clinical epidemiology is our colleagues at UpToDate, the electronic informa-
a “basic science for clinical medicine” and helped the tion source for clinicians and patients, we have been
world to understand. Many others have followed. We developing new ways to make the best available
are especially grateful for our work in common with evidence on real-world, clinical questions readily
Brian Haynes, founding editor of ACP Journal Club; accessible during the care of patients and to make that
Ian Chalmers, who made the Cochrane Collabora- evidence understandable not just to academicians and
tion happen; Andy Oxman, leader of the Rocky investigators, but to full-time clinicians as well.
Mountain Evidence-Based Healthcare Workshop; Ed Wagner was with us at the beginning of this
Peter Tugwell, a founding leader of the International project. With him, we developed a new course in clini-
Clinical Epidemiology Network (INCLEN); and cal epidemiology for the University of North Carolina
Russ Harris, our long-time colleague at the interface School of Medicine and wrote the first edition of this
between clinical medicine and public health at the book for it. Later, that course was Grant’s introduction
University of North Carolina. These extraordinary to this field, to the extent he had not already been intro-
people and their colleagues have created an exciting duced to it at home. Ed remained a coauthor through
intellectual environment that led to a revolution in three editions and then moved on to leadership of
clinical scholarship, bringing the evidence base for Group Health Research Institute and other responsi-
clinical medicine to a new level. bilities based in Seattle. Fortunately, Grant is now on
Like all teachers, we have also learned from our the writing team and contributed his expertise with the
students, clinicians of all ages and all specialties who application of clinical epidemiology to the current prac-
wanted to learn how to judge the validity of clini- tice of medicine, especially the care of very sick patients.
cal observations and research for themselves. Bob and We are grateful to members of the team, led by
Suzanne are grateful to medical students at McGill Lippincott Williams & Wilkins, who translated
University (who first suggested the need for this word processed text and hand-drawn figures into an
book), the University of North Carolina and Har- attractive, modern textbook. We got expert, personal
vard Medical School; fellows in the Robert Wood attention from Catherine Noonan, who guided us in
Johnson Clinical Scholars Program, the International the preparation of this book throughout; Jonathan
Clinical Epidemiology Network (INCLEN), and the Dimes, who worked closely with us in preparing illus-
Harvard General Medicine Fellowship; CRN Schol- trations; and Jeri Litteral, who collaborated with us in
ars in the Cancer Research Network, a consortium of the copy editing phase of this project.
research institutes in integrated health systems; and We are especially grateful to readers all over the
participants in the Rocky Mountain Evidence-Based world for their encouraging comments and practical
Healthcare Workshops. They were our students and suggestions. They have sustained us through the rig-
now are our colleagues; many teach and do research ors of preparing this, the fifth edition of a textbook
with us. Over the years, Grant has met many of these first published 30 years ago.
vii