Clinical Trials in RheumatoidArthritis and Osteoarthritis

Series Editors

Derek Pearson, BSc, PhD Colin G. Miller, PhD, FICRJoint Service Manager Senior Vice PresidentMedical Physics & Clinical Engineering Medical AffairsDepartment Bio-Imaging Technologies Inc.Nottingham University Hospitals NHS 826 Newtown-Yardley RoadTrust Newtown, PA 18940City Hospitals Campus USAHucknall NG5 1PBUK

Other Titles in This Series

Clinical Trials in Osteoporosis (2nd Edition)Derek Pearson and Colin G. Miller

Clinical Trials in Rheumatoid Arthritis and OsteoarthritisDavid M. Reid and Colin G. Miller

David M. Reid • Colin G. MillerEditors

Clinical Trials in RheumatoidArthritis and Osteoarthritis

123

EditorsDavid M. Reid, MBChB, MD, FRCP Colin G. Miller, BSc, PhD, FICRDepartment of Medicine and Therapeutics Bio-Imaging Technologies Inc.University of Aberdeen Newtown, PA, USAAberdeen, UK

ISBN: 978-1-85233-874-9 e-ISBN: 978-1-84628-742-8DOI: 10.1007/978-1-84628-742-8

British Library Cataloguing in Publication DataClinical trials in rheumatoid arthritis and osteoarthritis

1. Rheumatoid arthritis - Treatment 2. Osteoarthritis -Treatment 3. Clinical trials

I. Reid, David, 1951- II. Miller, Colin G., 1960-616.7’22060724

ISBN-13: 9781852338749

Library of Congress Control Number: 2007937490

c©2008 Springer-Verlag London LimitedApart from any fair dealing for the purposes of research or private study, or criticism or review, aspermitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced,stored or transmitted, in any form or by any means, with the prior permission in writing of the publish-ers, or in the case of reprographic reproduction in accordance with the terms of licences issued by theCopyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent tothe publishers.The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of aspecific statement, that such names are exempt from the relevant laws and regulations and therefore freefor general use.Product liability: The publisher can give no guarantee for information about drug dosage and applicationthereof contained in this book. In every individual case the respective user must check its accuracy byconsulting other pharmaceutical literature.

Printed on acid-free paper

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Contents

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1David M. Reid and Colin G. Miller

2 Historical and Current Perspectives on Management ofOsteoarthritis and Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . 5Shirish Dubey and Adewale O. Adebajo

3 Development of Biological Therapies for Inflammatory Arthritis . . . . . 37Neil Basu

4 Study Design and End Points for Rheumatoid Arthritis Trials . . . . . . . 51Pieter Geusens and Colin G. Miller

5 Study Design and End Points in Ankylosing SpondylitisClinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69Désirée van der Heijde

6 Trial Design and Outcomes in Osteoarthritis . . . . . . . . . . . . . . . . . . . . . . . 81Nigel Arden

7 Ethical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91Derek Pearson and Colin G. Miller

8 Organization of the Clinical Trial by the Sponsor . . . . . . . . . . . . . . . . . . 113Colin G. Miller

9 Organization of the Trial at the Investigator Site . . . . . . . . . . . . . . . . . . . 123Julie Shotton, David M. Reid, and Colin G. Miller

10 Role of the Imaging Core Laboratory in Rheumatoid Arthritis andOsteoarthritis Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135Mark D. Endres and Anna M. Baratelle

11 Biochemical Markers of Rheumatoid Arthritis and Osteoarthritis:Clinical Utility and Practical Considerations . . . . . . . . . . . . . . . . . . . . . . . 151Mario R. Ehlers and Elizabeth T. Leary

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vi Contents

12 Data Analysis and Presentation: Writing a Paper for Publication . . . . 171Derek Pearson

13 Radiographic Imaging End Points in Rheumatoid Arthritis Trials . . . . 201Anna M. Baratelle and Désirée van der Heijde

14 Radiography in Clinical Trials Investigating Osteoarthritis . . . . . . . . . . 223Cornelis van Kuijk

15 Use of Quantitative Magnetic Resonance Imaging in theCross-Sectional and Longitudinal Evaluation of Structural Changesin Knee Osteoarthritis Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235Jean-Pierre Raynauld, Johanne Martel-Pelletier, François Abram,and Jean-Pierre Pelletier

16 Biochemical Markers as Surrogate End Points of Joint Disease . . . . . . 249L. Stefan Lohmander and David R. Eyre

17 Role of Genetics and Genomics in Clinical Trials in Osteoarthritisand Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275Stuart H. Ralston

18 Cost-Effectiveness of New Biologics for Rheumatoid Arthritisand Osteoarthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289Yolanda Bravo Vergel and David Torgerson

Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311

Contributors

Adewale O. Adebajo, MBBS, MSc, FRCPHonorary Senior Lecturer, Academic Rheumatology Group, University of Sheffield,Sheffield UK

François Abram, PhDArthroVision Inc., Montreal, Canada

Nigel Arden, MBBS, MSc, MDSenior Lecturer in Rheumatology, MRC Unit, Southampton General Hospital,Southampton, UK

Anna M. Baratelle, ASRT, (R)(MR)Clinical Imaging Lead, Centocor, Malvern, Pennsylvania, USA. Previously,Director, Business Development and Clinical Education, Bio-ImagingTechnologies, Inc., Newtown, Pennsylvania, USA

Neil Basu, MBChB (Hons), MRCP(UK)Specialist Registrar, NHS Grampian, Aberdeen Royal Infirmary, Aberdeen, UK

Yolanda Bravo Vergel, BA, MA, MScResearch Fellow, Centre for Health Economics, University of York, York, UK

Shirish Dubey, MB, BS, MRCP (Ireland), DMedEdPreviously Clinical Lecturer in Rheumatology and Medical Education, AcademicUnit of Medical Education, University of Sheffield, Sheffield, UK

Mario R. Ehlers, MD, PhDChief Medical Officer, Pacific Biometrics, Inc., Seattle, Washington, USA

Mark D. Endres, BS, CNMTVice President, Global Business Development, Bio-Imaging Technologies, Inc.,Newtown, Pennsylvania, USA

David R. Eyre, BS, PhDDepartment of Orthopaedics and Sports Medicine, University of Washington,Seattle, Washington, USA

Pieter Geusens, MD, PhDDepartment of Rheumatology, University Hospital, Maastricht, The Netherlandsand Biomedical Research Institute, University Hasselt, Diepenbeek, Belgium

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viii Contributors

Elizabeth T. Leary, PhDChief Scientific Officer, Pacific Biometrics, Inc., Seattle, Washington, USA

L. Stefan Lohmander, MD, PhDInstitute of Clinical Sciences, Department of Orthopaedics, Lund UniversityHospital, Lund, Sweden

Johanne Martel-Pelletier, PhDOsteoarthritis Research Unit, Notre-Dame Hospital, University of MontrealHospital Centre (CHUM), Montreal, Canada

Colin G. Miller, BSc, PhD, FICRSenior Vice President, Medical Affairs, Bio-Imaging Technologies Inc., Newtown,Pennsylvania, USA

Derek Pearson, BSc, PhDClinical Director, Medical Physics, City Hospital, Nottingham, UK

Jean-Pierre Pelletier, MDOsteoarthritis Research Unit, Notre-Dame Hospital, University of MontrealHospital Centre (CHUM), Montreal, Canada

Stuart H. Ralston, MD, FRCP, FMedSci, FRSEHead of School of Molecular and Clinical Medicine & Professor of Rheumatology,Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK

Jean-Pierre Raynauld, MD, FRCPCOsteoarthritis Research Unit, Notre-Dame Hospital, University of MontrealHospital Centre (CHUM), Montreal, Canada

David M. Reid, MBChB, MD, FRCP edin, FRCP lonProfessor of Rheumatology, Head of Department of Medicine & Therapeutics,University of Aberdeen, Aberdeen, UK

Julie Shotton, BScPreviously Senior Research Nurse, Osteoporosis Research Unit, Department ofMedicine & Therapeutics, University of Aberdeen, Aberdeen, UK

David Torgerson, MSc, PhDDirector of York Trials Unit, Department of Health Sciences, University of York,York, UK

Désirée van der Heijde, MD, PhDProfessor of Rheumatology, Leiden University Medical Center, Departmentof Rheumatology, Leiden, The Netherlands

Cornelis van Kuijk, MD, PhDDepartment of Radiology, VU University Medical Center, Amsterdam,The Netherlands