Clinical Trials in Osteoporosis Second Edition

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Clinical Trials in Osteoporosis

Second Edition

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Clinical Trials in Osteoporosis

Second Edition

Edited by

Derek Pearson

and

Colin G. Miller

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British Library Cataloguing in Publication Data Clinical trials in osteoporosis - 2nd ed.

1. Osteoporosis - Chemotherapy - Research - Handbooks, manuals, etc. 2. Drugs - Testing - Handbooks, manuals, etc.

I. Pearson, Derek, 1954- II. Miller, Colin G., 1960- 616.7⬘16

Library of Congress Control Number: 2006931121

ISBN-10: 1-84628-389-2 2nd edition e-ISBN-10: 1-84628-587-9 2nd edition ISBN-13: 978-1-84628-389-5 2nd edition e-ISBN-13: 978-1-84628-587-5 2nd edition ISBN-10: 1-85233-229-8 1st edition

Printed on acid-free paper

Second edition 2007

Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted 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 publishers, or in the case of reprographic reproduction in accordance with the terms of licences issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers.

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use.

Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.

9 8 7 6 5 4 3 2 1

Springer Science+Business Media springer.com

Derek Pearson, BSc, PhD Joint Service Manager Medical Physics & Clinical

Engineering Department Nottingham University Hospitals

NHS Trust Nottingham UK

Colin G. Miller, PhD, FICR Sr. Vice President

Medical Affairs

Bio-Imaging Technologies Inc.

Newtown, PA USA

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v

Foreword to the First Edition

Before the mid-1990s, very few people were aware of the disease of osteoporosis, not only in the general population, but also in the medical profession. In the past 10 years there have been many advances and developments in the understanding of this crippling disease, to the point that this therapeutic field has lost its “fledg- ling” status and has grown up rapidly. This is well demonstrated by the number of effective therapies that are available, the new methodologies for the diagnosis and monitoring of the disease, and the fact that the importance of osteoporosis, as a disease, is now recognised and is taught as an integral part of the syllabus in most medical schools.

With the maturation of this therapeutic area, it has now become a challenge for physicians, scientists, and technologists to gain an easy understanding of the intri- cacies of running studies or clinical trials in osteoporosis. This book provides an excellent introduction and handbook for those wishing to pursue research in this field. It not only provides an overview of the field of osteoporosis, the measurement methodologies available, and current therapies, but also covers all the nec- essary regulations and good clinical practice requirements that are both specific to the disease state and generic across all clinical trials. Furthermore, an interesting slant has been taken in providing “mock trial data”. The reader is then taken through the analysis of the study and, rather than having to do this theoretically, can work with the data provided. It will then be very straightforward for the reader to apply the calculations derived to their own data.

This book has been written in an easy-to-read style, and novices to the field of osteoporosis and/or clinical trials will be guided through the whole process. It is unusual on two major accounts. First, it has been written to appeal to those working in the pharmaceutical industry, in addition to those at the trial site: principal investigators, study site coordinators, and bone densitometry technologists. This has been achieved by the inclusion of several guest chapters, so the whole clinical trial arena has been covered. Second, this book has been written with both European, American and Canadian markets in mind. The principal authors, although both British, live on opposite sides of the Atlantic, and so the book has a very comprehensive feel to it. This unusual meld of editors and authors, from both industry and academia, has provided a unique opportunity for the development of this book, encompassing the many facets of clinical trials in osteoporosis. The addition of several notable guest authors has increased the depth of this book.

As a physician who has been involved in the field of osteoporosis for many years, I believe that this book enters the marketplace in a timely manner. Because the field has matured, this reference work is needed to help the researcher obtain the principles of the disease and clinical trial environment in a rapid and convenient

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vi Foreword to the First Edition

manner. It answers most of the basic questions, and many of the more complex ones. Because it covers the clinical trial programme from start-up to data analysis and publication, it will become a very useful and widely used handbook. Although some will read it from beginning to end, it also lends itself to being dipped into at the appropriate points in a trial lifecycle, without having to be onerous on time, which is rarely available in great quantities to anyone involved in clinical trials.

Ignac Fogelman Guys Hospital, London, UK

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Contributors

Dr Dorothy Adams

Jackson Foundation, Madison, WI, USA Dr Jonathan R. Bayly

Faculty of Education, Health and Sciences, University of Derby, Derby, UK Dr Penny Blackwell

Clinical Chemistry, Nottingham University Hospitals NHS Trust, Nottingham, UK Mrs Susan A. Earnshaw

South Canterbury, New Zealand Professor Ignac Fogelman

Department of Nuclear Medicine, Guys Hospital, London, UK Dr Ian M. Godber

Biochemistry Department, Wishaw General Hospital, Wishaw, UK Professor David J. Hosking

Nottingham University Hospitals NHS Trust, Nottingham, UK Dr Nigel Lawson

Clinical Chemistry, Derby Hospital NHS Foundation Trust, Derby City General Hospital, Derby, UK

Dr Colin G. Miller

Senior Vice President, Medical Affairs, Bio-Imaging Technologies Inc., Newtown, PA, USA

Dr Derek Pearson

Medical Physics and Clinical Engineering, Nottingham University Hospitals NHS Trust, Nottingham, UK

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Contributor Biographies

Dorothy Adams is an experienced Research Administrator, having been involved in the running of numerous osteoporosis trials. She is an Executive Director of the Jackson Foundation, a clinical research organization based in Madison, WI, USA.

Jonathan R. Bayly is an associate lecturer at the University of Derby, Derby, UK, in the faculty of Education, Health and Sciences, where he works on the Radiography, Informatics, and Osteoporosis programme (http://www.derby.ac.uk/

osteoporosis/index.htm). He is also the lead clinician for the Gloucestershire Primary and Community Care Audit Group, Gloucestershire, UK (http://www.

glospccag.nhs.uk), supporting clinical governance in the three Primary Care Trusts within the county. He was a general practitioner for 20 years in Stroud, UK.

He is a member of the Royal College of General Practitioners, the American Society for Bone and Mineral Research, and the British Geriatrics Society and is on the scientific advisory group of the UK National Osteoporosis Society.

Penny Blackwell graduated from Birmingham University, Birmingham, UK, in biochemistry and trained in clinical biochemistry at Nottingham City Hospital, Nottingham, UK. She obtained her PhD in bone biochemistry in 2000, and is now a third-year medical student. She plays the French horn particularly well.

Susan A. Earnshaw was employed as a Superintendent Radiographer respon- sible for the bone densitometry service at Nottingham City Hospital, Nottingham, UK. She worked in this field for more than nine years, being involved with clinical subjects and more than 40 bone densitometry research trials. During this time, the development of the capability of dual-energy X-ray absorptiometry (DXA) machines to perform morphometric X-ray analysis (MXA) led to her pursuing and gaining an MPhil in spinal morphometry. She had strong links with the University of Derby (Derby, UK) distance-learning programme, writing about the practical aspects of DXA for the osteoporosis modules, and was also a module tutor. She is now living with her family in New Zealand, raising sheep!

Ian M. Godber is a graduate of the Universities of St Andrews and Dundee, Scotland, UK. Ian trained as a Clinical Biochemist at Ninewells Hospital in Dundee, during which time he completed an MSc at the University of Surrey, Guildford, UK.

He was a Senior Clinical Biochemist at Nottingham City Hospital, Nottingham, UK, in January 2000, where his main responsibilities included coordinating the biochemical analyses involved in a number of research projects investigating the

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biochemical markers of bone turnover and calcium homeostasis. He is currently Principal of Biochemist at Wishaw General Hospital in Wishaw, Scotland, and also edits the Association for Clinical Biochemistry website and the public infor- mation website for laboratory tests, Lab Tests Online UK.

David J. Hosking is a Consultant Physician at Nottingham City Hospital, Nottingham, UK. After postgraduate training in Birmingham, UK, he went to the University of Leiden, Leiden, the Netherlands as an Medical Research Council Travelling Fellow working in the Department of Endocrinology. His research interests are in the fields of osteoporosis, Paget’s disease, and vitamin D metabol- ism. He has published more than 100 papers in this field and is co-author of a textbook entitled Management of Metabolic Bone Disease.

Nigel Lawson graduated from the Biochemistry Department at the University of Sheffield, Sheffield, UK, in 1976, and obtained his PhD on the control of lipid synthesis from the University of Nottingham, Nottingham, UK, in 1980. After undertaking some more research in lipids, he worked in the Clinical Chemistry Departments of the East Birmingham Hospital and the Birmingham Children’s Hospital, plus the Regional Immunology Department, in Birmingham, UK. Nigel moved to the Clinical Chemistry Department at Nottingham City Hospital in 1991 to take up the post of Consultant Clinical Scientist and was made a Fellow of the Royal College of Pathologists in 1997. He is now working at the Derby Hospitals NHS Foundation Trust, Derby, UK.

Colin G. Miller graduated in 1983 from the University of Sheffield, Sheffield, UK, with a degree in physiology and zoology. He worked for four years as a Research Assistant at the Bio-Engineering Research Unit, Doncaster University, Doncaster, UK, and then as a Clinical Research Associate at Syntex Research, Department of Clinical Pharmacology and Therapeutics Investigation, Maidenhead, UK. During this time, he obtained a PhD from Hull University, Hull, UK, on the measurement of broadband ultrasonic attenuation for assessing hip fracture in the elderly. Since then, he has worked as a Clinical Research Coordinator at Norwich Eaton Limited (a Procter & Gamble Company) and as Head of the Physical Measurements Team, Europe, Procter & Gamble Pharmaceuticals, Egham, Middlesex, UK. Between 1991 and 1993, he worked on a part-time basis at Guys Hospital, London, UK, in the Department of Nuclear Medicine, working for Prof. Ignac Fogelman. From 1994, he was Director of Clinical Services at Bona Fide Ltd, Madison, Wisconsin, USA (a wholly owned subsidiary of the Lunar Corporation, Madison, Wisconsin, USA), taking up his current post as Vice President, Business Development, Bio-Imaging Technologies Inc., Newtown, Pennsylvania, USA in 1999, where he is now as Senior Vice President of Medical Affairs.

Derek Pearson graduated in Physics from Nottingham University, Nottingham, UK, in 1976. He obtained a PhD in medical physics from the University of Surrey, xii Contributor Biographies

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Guildford, UK and then spent three years as a postdoctoral fellow at the University of Leeds, Leeds, UK, working in the body composition group. He moved back to Nottingham in 1982 to work as a Senior Grade Physicist in nuclear medicine. He has been Clinical Director of Medical Physics at Nottingham City Hospital NHS Trust (now part of Nottingham University Hospitals NHS Trust, Nottingham UK) since 1989. He has a broad range of interests in imaging and radiation physics and has published more than 40 papers, most recently specializing in the measurement of bone density and bone imaging.

Contributor Biographies xiii

Clinical Trials in Osteoporosis Second Edition

Clinical Trials in Osteoporosis

Second Edition

Clinical Trials in Osteoporosis

Second Edition

Derek Pearson

Colin G. Miller

Foreword to the First Edition

Contents

Contributors

Contributor Biographies