1、CANCER CLINICAL TRIALS:PROACTIVE STRATEGIES Cancer Treatment and Research Steven T.Rosen,M.D.,Series Editor Sugarbaker,P.(ed):Peritoneal Carcinomarosis:Principles of Management.1995.ISBN 0-7923-3727-1.Dickson,R.B.,Lippman,M.E.(eds):Mammary Tumor Cell Cycle,Differentiation and Metastasis.1995.ISBN 0-
2、7923-3905-3.Freireich,E.J,Kantarjian,H.(4s):Molecular Genetics and Therapy of Leukemia.1995.ISBN 0-7923-3912-6.Cabanillas,F.,Rodriguez,M.A.(eds):Advances in Lymphoma Research.1996.ISBN 0-7923-3929-0.Miller,A.B.(ed.):Advances in Cancer Screening.1996.ISBN 0-7923-4019-1.Hait,W.N.(ed.):Drug Resistance.
3、1996.ISBN 0-7923-4022-1.Pienta,K.J.(ed.):Diagnosis and Treatment of Genitourinary Malignancies.1996.ISBN 0-7923-4164-3.Arnold,A.J.(4.):Endocrine Neoplasms.1997.ISBN 0-7923-4354-9.Pollock,R.E.(ed.):Surgical Oncology.1997.ISBN 0-7923-9900-5.Verweij,J.,Pinedo,H.M.,Suit,H.D.(eds):Soft Tissue Sarcomas:Pr
4、esent Achievements and Future Prospects.1997.ISBN 0-7923-991 3-7.Walterhouse,D.O.,Cohn,S.L.(eds):Diagnostic and Therapeutic Advances in Pediatric Oncology.1997.ISBN 0-7923-9978-1.Mittal,B.B.,Purdy,J.A.,Ang,K.K.(eds):Radiation Therapy.1998.ISBN 0-7923-9981-1.Foon,K.A.,Muss,H.B.(eds):Biological and Ho
5、rmonal Therapies of Cancer.1998.ISBN 0-7923-9997-8.Ozols,R.F.(ed.):Gynecologic Oncology.1998.ISBN 0-7923-8070-3.Noskin,G.A.(ed.):Management of Infectious Complications in Cancer Patients.1998.ISBN 0-7923-8150-5.Bennett,C.L.(ed.):Cancer Policy.1998.ISBN 0-7923-8203-X.Benson,A.B.(4.):Gastrointestinal
6、Oncology.1998.ISBN 0-7923-8205-6.Tallman,M.S.,Gordon,L.I.(eds):Diagnostic and Therapeutic Advances in Hematologic Malignancies.1998.ISBN 0-7923-8206-4.von Gunten,C.F.(ed.):Palliative Care and Rehabilitation of Cancer Patients.1999.ISBN 0-7923-8525-X Burt,R.K.,Brush,M.M.(4s):Advances in Allogeneic He
7、matopoietic Stem Cell Transplantation.1999.ISBN 0-7923-7714-1.Angelos,P.(ed.):Ethical Issues in Cancer Patient Care 2000.ISBN 0-7923-7726-5.Gradishar,W.J.,Wood,W.C.(eds):Advances in Breast Cancer Management.2000.ISBN 0-7923-7890-3.Sparano,J.A.(ed.):H N&HTLV-I Associated Malignancies.2001.ISBN 0-7923
8、-7220-4.Ettinger,D.S.(ed.):Thoracic Oncology.2001.ISBN 0-7923-7248-4.Bergan,R.C.(ed.):Cancer Chemoprevention.2001.ISBN 0-7923-7259-X.Ram,A,Mundle,S.D.(eds):Myelodysplastic Syndromes&Secondary Acute Myelogenous Leukemia 2001.ISBN:0-7923-7396.Talamonti,M.S.(ed.):Liver Directed Therapy for Primary and
9、Metastatic Liver Tumors.2001.ISBN 0-7923-7523-8.Stack,M.S.,Fishman,D.A.(eds):Ovarian Cancer.2001.ISBN 0-7923-7530-0.Bashey,A.,Ball,E.D.(4s):Non-Myeloablative Allogeneic Transplantation.2002.ISBN 0-7923-7646-3.Leong,S.P.L.(ed.):Atlas of Selective Sentinel Lymphadenectomy for Melanoma,Breast Cancer an
10、d Colon Cancer.2002.ISBN 1-4020-7013-6.Andersson,B.,Murray D.(4s):Clinically Relevant Resistance in Cancer Chemotherapy.2002.ISBN 1-4020-7200-7.Beam,C.(ed.):Biostatistical Applications in Cancer Research.2002.ISBN 1-4020-7226-0.Brockstein,B.,Masters,G.(eds):Head and Neck Cancer.2003.ISBN 1-4020-7336
11、-4.Frank,D.A.(ed.):Signal Transduction in Cancer.2003.ISBN 1-4020-7340-2.Figlin,R.A.(ed.):Kidney Cancer.2003.ISBN 1-4020-7457-3.Kirsch,M.;Black,P.McL.(ed.):Angiogenesis in Brain Tumors.2003.ISBN 1-4020-7704-1.Keller,E.T.,Chung,L.W.K.(eds):The Biology of Skeletal Metastases.2004.ISBN 1-4020-7749-1.Ku
12、mar,R.(4.):Molecular Targeting and Signal Transduction.2004.ISBN 1-4020-7822-6.Verweij,J.,Pinedo,H.M.(eds):Targeting Treatment of Soft Tissue Sarcomas.2004.ISBN 1-4020-7808-0.Finn,W.G.,Peterson,L.C.(eds.):Hematopathology in Oncology.2004.ISBN 1-4020-7919-2.Farid,N.(ed.):Molecular Basis of Thyroid Ca
13、ncer.2004.ISBN 1-4020-8106-5.Khleif,S.(ed.):Tumor Immunology and Cancer Vaccines.2004.ISBN 1-4020-81 19-7.Balducci,L.,Extermann,M.(4s):Biological Basis of Geriatric Oncology.2004.ISBN Abrey,L.E.,Chamberlain,M.C.,Engelhard,H.H.(eds):Leptomeningeal Metastases.2005.ISBN 0-387-24198-1 Platanias,L.C.(ed.
14、):Cytokines and Cancer.2005.ISBN 0-387-24360-7.Leong,S.P.L.,Kitagawa,Y.,Kitajima,M.(eds):Selective Sentinel Lymphadenectomy for Human Solid Cancer.2005.ISBN 0-387-23603-1.Small,Jr.W.,Woloschak,G.(4s):Radiation Toxicity:A Practical Guide.2005.ISBN 1-4020-8053-0.Haefner,B.,Dalgleish,A.(eds):The Link B
15、etween Inflammation and Cancer.2006.ISBN 0-387-26282-2.Leonard,J.P.,Coleman,M.(eds):Hodgkins and Non-Hodgkins Lymphoma.2006.ISBN 0-387-29345.Leong,S.P.L.(ed:)Cancer Clinical Trials:Proactive Strategies.2006.ISBN 0-387-33224-3.CANCER CLINICAL TRIALS:PROACTIVE STRATEGIES edited by STANLEY P.L.LEONG,MD
16、,FACS Professor and Director of Sentinel Lymph Node Program University of California Sun Francisco Medical Center at Mount Zion Sun Francisco,CA,USA a-springer Stanley P.L.Leong Department of Surgery University of California Medical Center at Mount Zion 1600 Divisadero Street San Francisco,CA 94143
17、leongssurgery.ucsf.edu CANCER CLINICAL TRIALS:PROACTIVE STRATEGIES Library of Congress Control Number:2006927192 ISBN-10:0-387-33224-3 e-ISBN-10:0-387-33225-1 ISBN-13:978-0387-33224-6 e-ISBN-13:978-0387-33225-3 Printed on acid-free paper.2007 Springer Science+Business Media,LLC All rights reserved.T
18、his work may not be translated or copied in whole or in part without the written permission of the publisher(Springer Science+Business Media,LLC,233 Spring Street,New York,NY 10013,USA),except for brief excerpts in connection with reviews or scholarly analysis.Use in connection with any form of info
19、rmation storage and retrieval,electronic adaptation,computer software,or by similar or dissimilar methodology now known or hereafter developed is forbidden.The use in this publication of trade names,trademarks,service marks and similar terms,even if they are not identified as such,is not to be taken
20、 as an expression of opinion as to whether or not they are subject to proprietary rights.While the advice and information in this book are believed to be true and accurate at the date of going to press,neither the authors nor the editors nor the publisher can accept any legal responsibility for any
21、errors or omissions that may be made.The publisher makes no warranty,express or implied,with respect to the material contained herein.Printed in the United States of America.9 8 7 6 5 4 3 2 1 Cover figure modified and printed with permission 2002 Coalition of Cancer Cooperative Groups.CONTENTS Contr
22、ibutors Foreword Preface Acknowledgement Historical Perspective and Evolving Concerns for Human Research Bernard Lo and Nesrin Garan Cancer Trials and the Institutional Review Board(IRB)Scott Kurtzman and Zita Lazzarini NCIs Cancer Therapy Evaluation Program:A Commitment to Treatment Trials Jeffrey
23、S.Abrams,Anthony Murgo and Michaele C.Christian Practical Guide for Cancer Clinical Investigators Steven Hirschfeld The Role of Cooperative Groups in Cancer Clinical Trials Ann M.Mauer,Elizabeth S.Rich and Richard L.Schilsky The Advocate Role in Clinical Study Development and Partnering with Patient
24、 Advocates in Your Local Institution Barbara Parker The National Breast Cancer Coalition:Setting the Standard for Advocate Collaboration in Clinical Trials Fran Visco The Role of the Principal Investigator in Cancer Clinical Trials Stanley P.L.Leong vii xiii xvii xix 1 11 3 1 5 1 11 1 131 143 157 VI
25、 9.The Audit Process and How to Ensure a Successful Audit 179 Y.Nancy You,Lisa Jacobs,Elizabeth Martinez and David M.Ota 10.The Privacy Rule(HIPAA)As It Relates To Clinical Research 199 John M.Harrelson and John M.Falletta 11.The Commission on Cancer,American College of Surgeons Response to HIPAA 20
26、9 E.Greer Gay 12.Ethical and Legal Issues in the Conduct of Cancer Clinical Trials 219 Gerianne J.Sands and Peggy A.Means 13.The Role of the Office of Research Integrity in Cancer Clinical Trials 231 Peter Abbrecht,Nancy Davidian,Samuel Merrill and Alan R.Price 14.Strategies for the Administration o
27、f a Clinical Trial Infrastructure:Lessons from a Comprehensive Cancer 241 Center Leonard A.Zwelling and Carleen A.Brunelli 15.The Clinical Research Process:Building a System in Harmony with Its Users 275 Greg Koski 16.Cancer Research and CHnical Trial in Action:An Important Exercise Before You Embar
28、k on Your Study 291 Stanley P.L.Leong,Larry Carbone and Scott Kurtzman Index 311 CONTRIBUTORS Peter Abbrecht,MD,PhD Medical Expert Office of Research Integrity Department of Health and Human Services Rockville,Maryland Jeffrey S.Abrams,MD NCI Project Officer Cancer Therapy Evaluation Program Divisio
29、n of Cancer Treatment and Diagnosis National Cancer Institute Bethesda,Maryland Carleen A.Brunelli,PhD,MBA Chief Research and Regulatory Affairs Officer Office of Research Administration The University of Texas M.D.Anderson Cancer Center Houston,Texas Larry Carbone,DVM,PhD Clinical Veterinarian Depa
30、rtment of Veterinary Medicine University of California San Francisco Medical Center San Francisco,California Michaele C.Christian,MD Associate Director Cancer Therapy Evaluation Program Division of Cancer Treatment and Diagnosis National Cancer Institute Bethesda,Maryland Nancy Davidian,PhD Clinical
31、 Case Expert Office of Research Integrity Department of Health and Human Services Rockville,Maryland Vlll John M.Falletta,MD IRB Chairman Institutional Review Board Professor of Pediatrics Duke University Health System Durham,North Carolina Nesrin Garan Program in Medical Ethics Department of Medici
32、ne University of California San Francisco San Francisco,California Greer Gay,RN,PhD,MPH Manager,Research Unit National Cancer Data Base Division of Research and Optimal Care American College of Surgeons Chicago,Illinois John M.Harrelson,MD Associate Professor Pathology/Orthopedic Surgery Director Mu
33、sculoskeletal Oncology Division Director Diabetic Foot Clinic Duke University Health System Durham,North Carolina Steven Hirschfeld,MD,PhD CAPT USPHS Office of Cellular,Tissue and Gene Therapy Center for Biologies Evaluation and Research Food and Drug Administration Rockville,Maryland Lisa Jacobs,MD
34、 Assistant Professor of Surgery Department of Surgery Johns Hopkins University Baltimore,Maryland Greg Koski,MD,PhD Associate Professor of Anesthesia Senior Scientist Institute for Health Policy Massachusetts General Hospital Harvard Medical School Boston,Massachusetts IX Scott Kurtzman,MD,FACS Dire
35、ctor of Surgery Waterbury Hospital Waterbury,Connecticut Department of Surgery University of Connecticut School of Medicine Farmington,Connecticut Zita Lazzarini,JD Division Director and Associate Professor Department of Surgery University of Connecticut School of Medicine Farmington,Connecticut Sta
36、nley P.L.Leong,MD,FACS Professor and Director,Sentinel Lymph Node Program Department of Surgery University of California San Francisco Medical Center at Mount Zion Member,UCSF Comprehensive Cancer Center,San Francisco,California Bernard Lo,MD Professor Program in Medical Ethics Department of Medicin
37、e University of California San Francisco San Francisco,California Elizabeth Martinez,LPN,BS Lead Auditor American College of Surgeons Oncology Group Durham,North Carolina Ann M.Mauer,MD Assistant Professor of Medicine Cancer and Leukemia Group B Central Office of the Chairman Chicago,Illinois Peggy
38、A.Means Consultant Fred Hutchinson Cancer Research Center Seattle,Washington Samuel Merrill,PhD Scientist-Investigator Office of Research Integrity Department of Health and Human Services Rockville,Maryland Anthony Murgo,MD Acting Chief Investigational Drug Branch Associate Chief for Developmental C
39、hemotherapy Evaluation Program Cancer Therapy Evaluation Program Division of Cancer Treatment and Diagnosis National Cancer Institute Bethesda,Maryland David M.Ota,MD Department of Surgery Duke University Medical Center Durham,North Carolina American College of Surgeons Oncology Group Durham,North C
40、arolina Barbara Parker Breast Cancer SPORE and American College of Surgeons Oncology Group Duke University Medical Center Durham,North Carolina Alan R.Price,PhD Associate Director for Investigative Oversight Office of Research Integrity Rockville,Maryland Elizabeth S.Rich,MD,PhD Assistant Professor
41、of Medicine Cancer and Leukemia Group B Central Office of the Chairman Chicago,Illinois Gerianne J.Sands Associate General Counsel Fred Hutchinson Cancer Research Center Seattle,Washington XI Richard L.Schilsky,MD Professor of Medicine Cancer and Leukemia Group B Central Office of the Chairman Chica
42、go,Illinois Fran Visco President National Breast Cancer Coalition Washington,DC Y.Nancy You,MD Surgical Research Fellow American College of Surgeons Oncology Group Durham,North Carolina Leonard A.Zwelling,MD,MBA Vice President for Research Administration Office of Research Administration The Univers
43、ity of Texas M.D.Anderson Cancer Center Houston,Texas FOREWORD Samuel A.Wells,Jr.,MD Professor of Surgery Duke University Medical Center Durham,North Carolina The formal organization of a clinical trial program for the treatment of patients with malignant diseases began in this country over 50 years
44、 ago and resulted in a large part from the availability of promising therapeutic agents for the treatment of leukemia,and subsequently solid tumors.The National Cancer Institute(NCI)initiated this effort,which has gradually expanded to include twelve cooperative clinical trial groups involving 1700
45、institutions in Canada,Europe and the United States.The cooperative groups,administered by the Cancer Therapy Evaluation Program of the NCI,enter over 22,000 patients on clinical studies each year.The groups are large and complex organizations that include a number of specialists,such as:clinical on
46、cologists,statisticians,other medical specialists,basic scientists,nurses,epidemiologists,health services researchers,data managers,information technologists,auditors,data and safety monitoring committee members,and patient advocates.Additional cancer clinical trials are supported by investigator-in
47、itiated grants or by the NO1 contract mechanism.The individual groups have conducted highly important clinical trials,which have substantially improved the treatment of patients with cancer.To appreciate the contributions of the cooperative group program,one need only review the accomplishments of t
48、he National Surgical Adjuvant Breast Project,which greatly improved the management of patients with carcinoma of the breast,or the role of the Childrens Cancer Group and the Pediatric Oncology Group(now combined as the Childrens Oncology Group),which reduced the mortality of childhood cancer(Figure
49、IA)despite an increasing incidence(Figure 1B).The pediatric clinical trial groups have had a remarkable impact on the survival of children with cancer,due in a large part to their ability to accrue over half of children with cancer in the U.S.and Canada to their clinical trials,a rate more than ten
50、times that achieved by the adult cooperative groups.XIV Dr.Leong has edited and authored an important book on Cancer Clinical Trials:Proactive Strategies.There are contributions from a series of international experts on clinical trials.This book provides an important historical context and thoroughl
