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Textbook of Clinical Trials TextbookofClinicalTrials. EditedbyD.Machin,S.DayandS.Green 2004JohnWiley&Sons,Ltd ISBN:0-471-98787-5 Textbook of Clinical Trials Editedby David Machin DivisionofClinicalTrialsandEpidemiologicalSciences, NationalCancerCentre,SingaporeandUKChildren’sCancerStudyGroup, UniversityofLeicester,UK. Simon Day MedicinesandHealthcareproductsRegulatoryAgency, London,UK Sylvan Green ArizonaCancerCentre,Tucson,Arizona,USA SectionEditors Brian Everitt InstituteofPsychiatry,London,UK Stephen George DepartmentofBiostatisticsandInformatics, DukeUniversityMedicalCentre,Durham,NC,USA Copyright2004 JohnWiley&SonsLtd,TheAtrium,SouthernGate,Chichester, WestSussexPO198SQ,England Telephone(+44)1243779777 Email(forordersandcustomerserviceenquiries):[email protected] VisitourHomePageonwww.wileyeurope.comorwww.wiley.com AllRightsReserved.Nopartofthispublicationmaybereproduced,storedinaretrievalsystemortransmittedinany formorbyanymeans,electronic,mechanical,photocopying,recording,scanningorotherwise,exceptunderthetermsof theCopyright,DesignsandPatentsAct1988orunderthetermsofalicenceissuedbytheCopyrightLicensingAgency Ltd,90TottenhamCourtRoad,LondonW1T4LP,UK,withoutthepermissioninwritingofthePublisher.Requeststo thePublishershouldbeaddressedtothePermissionsDepartment,JohnWiley&SonsLtd,TheAtrium,SouthernGate, Chichester,WestSussexPO198SQ,England,[email protected],orfaxedto(+44)1243770620. 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ISBN0-471-98787-5(alk.paper) 1.Clinicaltrials.I.Machin,David. R853.C55T492004 610(cid:1).72(cid:1)4–dc22 2003065147 BritishLibraryCataloguinginPublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary ISBN0-471-98787-5 Typesetin10/12ptTimesbyLaserwordsPrivateLimited,Chennai,India PrintedandboundinGreatBritainbyAntonyRoweLtd,Chippenham,Wiltshire Thisbookisprintedonacid-freepaperresponsiblymanufacturedfromsustainableforestry inwhichatleasttwotreesareplantedforeachoneusedforpaperproduction. Contents Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 Brief History of Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 S. Day and F. Ederer 2 General Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 David Machin 3 Clinical Trials in Paediatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Johan P.E.Karlberg 4 Clinical Trials Involving Older People . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Carol JaggerandAntony J. Arthur 5 Complementary Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 P.C.Leung CANCER 85 6 Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 Donald A. Berry, Terry L.Smith and Aman U. Buzdar 7 Childhood Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Sharon B. Murphy and Jonathan J. Shuster 8 Gastrointestinal Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Dan Sargent, RichGoldberg and PaulLimburg 9 Haematologic Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141 Charles A. Schiffer andStephen L.George vi CONTENTS 10 Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 P.-Y.Liu andVernon K.Sondak 11 Respiratory Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 KyungmannKim CARDIOVASCULAR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 12 Cardiovascular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 LawrenceFriedmanand Eleanor Schron DENTISTRY AND MAXILLO-FACIAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 13 Dentistry and Maxillo-facial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 May C.M.Wong, Colman McGrathand EdwardC.M.Lo DERMATOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 14 Dermatology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 Luigi Naldi and CosettaMinelli PSYCHIATRY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 15 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 B.S. Everitt 16 Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 LeonJ. Thaland Ronald G. Thomas 17 Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 M. Katherine Shear andPhilip W. Lavori 18 Cognitive Behaviour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273 Nicholas Tarrier and TilWykes 19 Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 Graham Dunn REPRODUCTIVE HEALTH. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 20 Contraception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315 Gilda Piaggio 21 Gynaecology and Infertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 Siladitya Bhattacharya and Jill Mollison RESPIRATORY 357 22 Respiratory 359 Anders Ka¨lleń Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401 Contributors TONY ARTHUR School of Nursing, Faculty of Medicine and Health Sciences, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK, Email: [email protected] DONALD BERRY Department of Biostatistics, UTMD Anderson Cancer Centre, 1400 Holcombe Blvd, Box 447, Houston, TX 77030, USA, Email: [email protected] S. BHATTACHARYA Department of Obstetrics and Gynaecology, Aberdeen Maternity Hospital, Cronhill Road, Aberdeen AB25 2ZD, UK, Email: [email protected] ARMAN BUZDAR Department of Breast Medical Oncology, The University of Texas, M.D. Anderson Cancer Centre, Texas, USA SIMON DAY Licensing Division, Medicines and Healthcare products Regulatory Agency, Room 13-205 Market Towers, 1 Nine Elms Lane, London SW8 5NQ, UK, Email: [email protected] GRAHAM DUNN Biostatistics Group, School of Epidemiology and Health Sciences, Stopford Building, Oxford Road, Manchester M13 9PT, UK, Email: [email protected], [email protected] FRED EDERER The EMMES Corporation, 401 North Washington Street, Suite 700, Rockville, MD 20850, USA, Email: [email protected] viii CONTRIBUTORS BRIAN EVERITT Box 20, Biostatistics Department, Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK, Email: [email protected] LARRY FRIEDMAN National Heart, Lung, and Blood Institute, Building 31, Room 5A03, Bethesda, MD 20892 2482, USA, Email: [email protected] STEPHEN GEORGE Department of Biostatistics and Bioinformatics, Duke University Medical Centre, Durham, NC 27710, USA, Email: [email protected] RICH GOLDBERG Medical Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA, Email: [email protected] SYLVAN GREEN Arizona Cancer Centre, 1515 N Campbell Ave, PO Box 245024, Tucson, AZ 85724, USA, Email: [email protected] CAROL JAGGER Trent Institute for HSR, Department of Epidemiology and Public Health, University of Leicester, 22–28 Princess Road West, Leicester LE1 6TP, UK, Email: [email protected] ANDERS KA¨LLEŃ AstraZeneca R&D, Lund, Sweden, Email: [email protected] JOHAN KARLBERG Clinical Trials Centre, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China, Email: [email protected] KYUNGMANN KIM Department of Biostatistics & Medical Informatics, University of Wisconsin, 600 Highland Avenue, Box 4675, Madison, WI 53792, USA, Email: [email protected] PHILIP LAVORI VACSPCC (151K), 795 Willow Road, Menlo Park, CA 94025 2539, USA, Email: [email protected] P.C. LEUNG Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Room 74026, 5th Floor, Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong, Email: [email protected] PAUL LIMBURG Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA, Email: [email protected] CONTRIBUTORS ix P.Y. LIU SWOG Statistical Centre, MP 557, Fred Hutchinson Cancer Research Centre, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109 1024, USA, Email: [email protected] EDWARD LO Dental Public Health, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Hong Kong, Email: [email protected] DAVID MACHIN Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610, Singapore, Email: [email protected], [email protected] COLAMN MCGRATH Dental Public Health, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Hong Kong, Email: [email protected] COSETTA MINELLI Medical Statistics Group, Department of Epidemiology and Public Health, University of Leicester, 22–28 Princess Road West, Leicester LE1 6TP, UK, Email: [email protected] JILL MOLLISON Department of Public Health, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK, Email: [email protected] SHARON B. MURPHY Children’s Cancer Research Institute, The University of Texas Health Science Centre at San Antonio, 7703 Floyd Curl Drive, MC 7784, San Antonio, TX 78229-3900, USA, Email: [email protected] LUIGI NALDI Clinica Dermatologica, Ospedali Riuniti, L.go Barozzi 1, 24100 Bergamo, Italy, Email: [email protected] GILDA PIAGGIO Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organisation, 1211 Geneva 27, Switzerland, Email: [email protected] DANIEL SARGENT Mayo Clinic, 200 First Street, SW, Kahler 1A, Rochester, MN 55905, USA, Email: [email protected] CHARLES SCHIFFER Division of Oncology and Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA. ELEANOR SCHRON National Heart, Lung, and Blood Institute, Bethesda, MD 20892 2482, USA, Email: [email protected] x CONTRIBUTORS KATHERINE SHEAR Panic Anxiety and Traumatic Grief Program, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, Pittsburgh, PA 15213, USA, Email: [email protected], [email protected] JON SHUSTER PO Box 100212, College of Medicine, University of Florida, Gainesville, FL 32610 0212, USA, Email: [email protected]fl.edu TERRY SMITH UTMD Anderson Cancer Centre, 1400 Holcombe Blvd, Box 447, Houston, TX 77030, USA, Email: [email protected] VERNON K. SONDAK University of Michigan Medical Centre, Division of Surgical Oncology, 1500 E Medical Centre Drive, 3306 Cancer/Geriatrics Ctr Box 0932, Ann Arbor, MI 48109 0932, USA, Email: [email protected] NICHOLAS TARRIER University of Manchester, Academic Division of Clinical Psychology Education & Research Building, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK, Email: [email protected] LEON THAL Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92037, USA, Email: [email protected] RONALD THOMAS Department of Family and Preventative Medicine, and Neurosciences, UCSD 9500 Gilman Drive, La Jolla, CA 92039 0645, USA, Email: [email protected] MAY C.M. WONG Dental Public Health, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Hong Kong, Email: [email protected] TIL WYKES Department of Psychiatry, De Crespigny Park, London SE5 8AF, UK, Email: [email protected]