Designing Clinical Research An Epidemiologic Approach Second Edition By STEPHEN B. HULLEY, m.p., M.P.H. Professor and Chair, Department of Epidemiology & Biostatistics University of Calfomia, San Francisco STEVEN R. CUMMINGS, wp. Professor of Medicine and of Epidemiology & Biostatistics Assistant Dean for Clinical Research University of Catiforia, San Francisco WARREN S. BROWNER, o.v., M.v.H. Professor of Medicine and of Epidemiology & Biostatistics Chief, Genera! intemal Madicins Section San Francisco Veterans Affairs Meaicai Center University of Catifomia, San Francisco DEBORAH GRADY, mwv., M.r.H. Professor of Epidemiology & Biostatistics and of Medicine Staff Physician, Medical Service San Francisco Veterans Affairs Medical Center University of Catifomnia, San Francisco NORMAN HEARST, m.v., MPH. Profassor of Family & Community Medicine and of Epidemiology & Biostatisiics Attending Physician. Department of Family & Community Medicine University of California, San Francisco THOMAS B. NEWMAN, .n., M-v.it. Professor of Epidemiology & Biostatistics, of Pediatrics, and of Laboratory Medicine Attending Physician. Department of Peciairics University of Califomia, Son Francisco aM LIPPINCOTT. WALLIAMS & WILKINS A Wolters Kluwer Company Philadelphia - Baltimore + New York + Londen Buenos Aires + Hong Kong » Sydney + TokyoAcquisitions Ediior: Timothy ¥, Hiscock Desetopmesial dior Joyce A. Starphy Production Katior: John ©. Vassitiow Manufacturing Manager: Benjamin Rivera Gower Designer: Mark. Lerner Compositor: The PRE Group/BiComp. Printer: RR Donnelley, Crafordwville 2001 by LIPPINCOTT WILLIAMS & WILKINS SM Walnut Street Philadelphia, PA (9106 USA LWW.com All rights reserved, his book is pratecced by copyright No purt of this book: may be reproduced in aay form or by any mevas, including photocopying, or uuiized by any anformation storage and retrieval system wittiout writen petatisuon {rani the copyrigial owner, exeepl for brief quotations embodied ia stitial articls and reviews. Matcvials appearing in this book prepared by individuals 2s part of their official duties as US. governarent employers are nol cavered by the nbove-memtioned eanyriight Printed in the USA, Library of Congress Cataloging-n-Publication Data Desizting clinical research : un epidemiologic approach J by Stephen B. Hulley etal. dnd ed, psn. Includes hiMfiographical references and index. ISBN (7817-22187 1, Clinical trials—Technique. 2, Medicine Research: Methodology. 3 Epidensiology—Research—Methedategy. [ Hulley. Stephen B. JDNLM! 1, Epidemiologic Methinis. 2. Resesrsh Design, WA 951) DAS? 200) RADACSS 47 2001 oun deat oo-zats Care has been taken to confirm the occuragy of the informntion presented nd to describe generally accepted practices, However. the authors, ediiars, and publisher are not responsible lor errors er omissions or for any consequences fron application of the intarmation in this book and make no warranty, ‘expressed or implied, with respect to the eurreney, completeness, or accuracy of the contents of the publication. Application of this information in u purticul sitsution remains the professional responsibility of (he practitioner The authors. editors, and publisher have exerted every effort ty ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice al the Ge of pubbeation, However, in view of ‘ongoing rescarch, changes in government regulatioas, and the eoristamt Now of information relating 10 drug therapy and drug reactions, the wader is urged to teheck the packige insert for each drug for any chunge in indications anu! dasige and for added warnings and precautions. ‘Chis is parbcularty important when the recommended agent. is a new or infrequently employed drug. Some drugs and medical deviees presented in this publication have Food aad Drug Administration (FDA) clearance for limited use i restricted rescarch suttings. [tis the responsihility of the health care provider to ascertain the TDA status of each deug ar device planncd far use in their clinival practice WOATOSAZIEContents Introduction .. 2... Acknowledgments Section I: Basic Ingredients 1 vi Getting Started: The Anatomy and Physiology of Clinical RESECICA eee Stephen B. Hulley, Thomas 8, Newman, and Steven R. Cummings The Anatomy of Research: What It's Made of Tne Physiology of Research: How it Works. . Designing the Study . Summary Exercises Appendix: Study Outing Conceiving the Research Question, Steven R. Cummings, Warren $. Browner, and Stephen 8, Hulley Origins of a Research Question : Characteristics of G Good Research Question Developing the Research Question and Study Plan. Summary Exercises . Choosing the Study Subjects: Specification, Sampling. and Recrullment oe Stephen 8. Hulley, Thomas B. Newman, and Steven R. Cummings Basic Teims and Concepts Selection Criteria sampling Recruitment. summary Exercises . Appendix: Drawing @ Random Sample xi aw. 12 12 4 15 v "7 19 21 22 23 28 25 27 30 3 33 33. 38