Global Clinical Trials for Alzheimer's Disease. Design, Implementation, and Standardization

391 Pages·2014·9.04 MB·English

by  Menghis Bairu and Michael Weiner (Eds.)

GLOBAL
CLINICAL
TRIALS FOR
ALZHEIMER’S
DISEASE
Design, Implementation, and
Standardization
Edited by
Menghis Bairu, md
President and Chief Executive Officer
Speranza Therapeutics Corp, Dublin, Ireland
Chief Medical Officer and Head of Global Development
Elan Pharmaceuticals
Cambridge, Massachusetts, USA
Michael W. Weiner, md
Director of the Magnetic Resonance Unit at the VA Medical Center
Professor of Radiology, Medicine, Psychiatry and Neurology
University of California at San Francisco, School of Medicine
San Francisco, California, USA
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International Editorial Advisors
GLOBAL CLINICAL TRIALS FOR ALZHEIMER’S
DISEASE
Edited by
Menghis Bairu & Michael W. Weiner
Saleh A. Bawazir PhD
Vice President for Drug Affairs, Saudi Food and Drug Authority,
and Professor of Clinical Pharmacy, College of Pharmacy, King Saud
University, Riyadh, Saudi Arabia
Suzanne Gagnon MD, FACP
Chief Medical Officer, NuPathe Inc., Pennsylvania, USA
Douglas Love BS, JD
Executive Vice President, Head of Tysabri, Elan Pharmaceuticals,
San Francisco, USA
Michael Makanga MD, PhD
Director South-South Cooperation and Head of Africa Office,
European & Developing Countries Clinical Trials Partnership Tygerberg
Cape Town, South Africa
Rubin Minhas MD
Editor-in-Chief: ‘Clinical Evidence’, ‘Best Practice’ & Clinical Director,
BMJ Evidence Centre, London, UK
Fidela Ll. Moreno MD
Visiting Professor, Faculty of Medicine and Surgery, University of Santo
Tomas and Former Vice President, Global Clinical Site Management and
Monitoring, Allergan Inc., USA
S.D. Seth MD, FAMS, FNASc, FIPS, FCAI, FISCD
Advisor, Clinical Trials Registry - India, National Institute of Medical
Statistics, Indian Council of Medical Research, Ansari Nagar,
New Delhi, India
Praise for Global Clinical Trials for Alzheimer’s Disease: Design,
Implementation, and Standardization
Edited by Menghis Bairu, MD and Michael W. Weiner, MD
Global Editorial Board Members: Ezio Giacobini, Jean Georges, Maria
Carillo, Michael Grundman, Marc Wortmann and Susan Abushakra
“Alzheimer’s disease is among the most critical problems facing the
world’s aging populations. For this global epidemic, we need not a
few national plans, but rather a well-coordinated, ambitious interna-
tional plan. This book, written by outstanding experts in AD clinical tri-
als, surveys the landscape and lays down the groundwork essential for
progress.”
—Paul Aisen, MD, Director, Alzheimer’s Disease Cooperative Study
and Professor, Department of Neurosciences, University of California,
San Diego, School of Medicine, San Diego, CA
“Alzheimer’s disease is quite possibly the largest worldwide medical
problem of this decade. Despite a great deal of research and discussion
about the disease in the U.S. and Europe, a global solution to mak-
ing progress in the field is seldom discussed. Global Clinical Trials for
Alzheimer’s Disease is an excellent resource for anyone interested in solv-
ing the Alzheimer’s Disease challenge as it offers real world solutions to
achieving successful clinical trials globally.”
—Dale Schenk, PhD, President and CEO of Prothena Corporation, San
Francisco, CA
“Alzheimer’s disease is rapidly becoming perhaps the most important
disease in modern society. Development of new therapies for this disease
is a very important yet challenging task. This book covers every aspect of
the field and will doubtlessly become the seminal textbook for the devel-
opment of new therapies for Alzheimer’s disease.”
—Richard Chin, MD, CEO, Kindred Bio, Burlingame, and Associate
Professor, University of California, San Francisco School of Medicine,
San Francisco, CA
Preface
Alzheimer’s Disease (AD) is the 21st Century epidemic. Today, nearly
35 million individuals worldwide live with Alzheimer’s-related demen-
tia. By 2050, that number will more than triple to 115 million, a poten-
tially catastrophic global challenge already impacting families, social
service and healthcare delivery systems in every nation on earth. In 2010,
Alzheimer’s-related costs were estimated at $604 billion, approximately
one percent of the world’s GDP, and rising. AD impacts far more than
the individual victim: family members, the first line of care in much of
the world, suffer additional billions in lost income and life opportunities.
In 2011, President Barak Obama could have been addressing an audi-
ence far beyond the U.S. borders when he declared, “… Alzheimer’s
Disease burdens an increasing number of our elders and their families. It
is essential that we confront the challenge it poses to our public health.”
Time grows short. Of the 193 World Health Organization (WHO)
member nations, fewer than 10 have implemented comprehensive
national AD strategies, all of which are developed countries. Despite bil-
lions invested in research, and a clearer understanding, for example, of
AD’s etiology and pathology, no cure or effective treatment is in sight.
Sixty percent of Alzheimer’s victims—the majority still undiag-
nosed—live in lesser developed countries; by 2030, that figure will top
75 percent, with the heaviest burden on Africa, Asia, and Latin America.
Like the disease itself, the clinical trials vital to AD advances will take
place in the developing world. Here, too, the clock is ticking, with much
of the groundwork—including addressing the stigma so often associated
with the disease—still to be done.
Global Clinical Trials for Alzheimer's Disease: Design, Implementation,
and Standardization provides a clear blueprint for the road ahead. It is a
comprehensive, yet detailed analysis—drawing on the knowledge and
insight of the world’s leading experts—of the benefits, challenges, costs,
design, implementation, standardization, ethics, efficacy, and regulatory
considerations necessary to conduct effective Alzheimer’s trials in the
developing world. From the field, researchers and public health officials
review decades of clinical studies, as well as strategies being developed
in Latin America, India, China, Korea, Turkey, and elsewhere; lessons
that provide invaluable insight and hands-on experience for the next
generation of AD researchers.
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PREFACE
Global Clinical Trials for Alzheimer’s Disease is also a call to action. The
great challenge of the next decades will be to find the resources, finan-
cial and humanitarian, to better care for those afflicted with AD, and to
refine and redouble research efforts to develop new therapies, and hope-
fully, the cure. As we see in these pages, this will require a collabora-
tion of all stakeholders—academia, the pharmaceutical industry, public
health organizations both domestic and international, and, foremost, the
patients in the developing world who will be both subjects as well as the
measurement of our success in the difficult battle ahead.
Menghis Bairu
Michael W. Weiner
About the Editors
Menghis Bairu, M.D.—physician, editor,
author, philanthropist and healthcare business
executive—has more than two decades of inter-
national experience in the biotechnology, phar-
maceutical, global health and non-profit arenas.
Dr. Bairu serves as Executive Vice President,
Chief Medical Officer and Head of Global
Development at Elan. His responsibilities
include, but are not limited to clinical develop-
ment, biometrics, regulatory, CMC, QA, safety-
and-risk management, clinical operations and
medical affairs. Previously he served as head of
Onclave Therapeutics, a wholly Elan-owned oncology biotech company.
He lectures extensively on global health and biopharmaceutical issues
with particular focus on Emerging Markets (e.g. India, China, Latin
America, Singapore, Middle East, South East Asia and Africa). He served
as editor and co-author of Global Clinical Trials: Effective Implementation
and Management (Elsevier, 2011), a textbook designed to help research-
ers develop and implement effective and ethical international clinical
trials. Dr. Bairu is also editor/co-author of Global Clinical Trials Playbook:
Management and Implementation (Elsevier, 2012).
Prior to joining Elan, Dr. Bairu worked at Genentech for more than
five years in a number of managed care, medical and commercial
(Oncology, Immunology, and Cardiovascular) roles. He served as man-
aged care Medical Director for Fremont Health Corporation/II before
joining Genentech. He served on the board of directors for One World
Health, a nonprofit drug development company funded by the Bill and
Melinda Gates Foundation and A-Cube, a privately held pharma startup.
In 2013, Dr. Bairu was named to the boards of directors of Dubai-
based NewBridge Pharmaceuticals (he also serves as chairman of
NewBridge’s science and technology committee), and ADVentura
Capital SL, a Barcelona, Spain-based venture capital firm focused on
funding and mentoring promising healthcare, IT and GreenTech com-
panies. In 2011, Dr. Bairu joined the advisory board of the China Trials
5, a global clinical trials development summit focusing on China and
north Asia. He currently serves as Adjunct Faculty at the University of
California San Francisco School of Medicine where he lectures on global
clinical trials’ design, development and conduct.
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ABOUT THE EDITORS
Dr. Michael W. Weiner attended Johns
Hopkins University and the State University
of New York, and worked at Mount Sinai
Hospital in New York (Resident), and Yale
University (Fellow). After service in the US Air
Force, in 1971 at the University of Wisconsin he
was awarded a VA Research Associate at the
Madison VA. Subsequently he was awarded
a VA Clinical Investigatorship and relocated
to the Palo Alto VA/Stanford University,
where he received the Young Investigator
Award of the American College of Cardiology
in 1976. In 1980 he performed the first experiment using implanted
coils to obtain 31P NMR spectra from the kidney of living rats, begin-
ning his work using NMR/MRI for research. Since 1980 he has been
at the San Francisco VA/UCSF. Dr. Weiner is currently Director of the
Center for Imaging of Neurodegenerative Diseases. He is Professor of
Radiology, Medicine, Psychiatry, and Neurology at UCSF. He has pub-
lished over 600 peer reviewed scientific papers. His grants include stud-
ies of Alzheimer’s Disease, vascular dementia, frontotemporal dementia,
HIV/AIDS, gulf war illness, posttraumatic stress disorder, traumatic
brain injury, amyotrophic lateral sclerosis, epilepsy, and other neuro-
degenerative conditions. He is the Principal Investigator of: the NIA
funded Alzheimer’s Disease Neuroimaging Initiative (ADNI)/Grand
Opportunities (GO) Grant, and the renewal of ADNI (total funding over
$150 million for these 3 grants). Recently he was awarded a grant from
the DOD entitled Effects of traumatic brain injury and post traumatic stress
disorder on Alzheimer’s Disease in Veterans using ADNI. In 2006, Dr. Weiner
was awarded the Middleton Award, for outstanding research in the VA.
He was awarded the Gold Medal of Paul Sabatier University in Toulouse
France, and the Gold Medal of the city of Toulouse, France in 2010. In
2011 he accepted the Ronald and Nancy Reagan Research Award from
the Alzheimer’s Association on behalf of ADNI. In 2013, Dr. Weiner was
awarded the Potamkin Prize for Research in Pick’s, Alzheimer’s, and
Related Diseases from The American Academy of Neurology and The
American Brain Foundation.
List of Contributors
Susan Abushakra Élan Pharmaceuticals, San Francisco, California, USA
Ricardo F. Allegri MD, PhD, FAAN Aging and Memory Center, Neurological
Research Institute, Buenos Aires, Argentina
H. Michael Arrighi PhD Janssen Research and Development, South San
Francisco, California, USA
Pablo M. Bagnati Aging and Memory Center, Neurological Research Institute,
Buenos Aires, Argentina
Menghis Bairu MD Chief Medical Officer and Head of Global Development,
Elan Pharmaceuticals, Cambridge, Massachusetts, USA and President and
Chief Executive Officer, Speranza Therapeutics Corp, Dublin, Ireland
Sonia Brucki MD Department of Neurology, University of São Paulo School of
Medicine, Sao Pãulo, Brazil
Tal Burt MD Duke Global Proof-of-Concept Research Network, Duke Clinical
Research Unit and Duke Clinical Research Institute, Department of Psychiatry
and Behavioral Sciences, Duke University, Durham, North Carolina, USA
Lorne Cheeseman Anidan Inc, Irvine, California, USA
Richard Chin MD Kindred Bio, Burlingame, San Francisco, California, USA
Debbie N. Cote Debbie Cote Associates, California, USA
Jeffrey Cummings MD Cleveland Clinic Lou Ruvo Center for Brain Health,
Las Vegas, Nevada, USA
Stephanie Danandjaja MD Sanofi, Singapore
P. Murali Doraiswamy MD Departments of Psychiatry and Medicine, and the
Duke Institute for Brain Sciences, Duke University, Durham, North Carolina, USA
Murat Emre MD Department of Neurology, Istanbul University Faculty of
Medicine, Istanbul, Turkey
James (Dachao) Fan MD, MBS ICON Clinical Research, Singapore
Yoko Fujimoto PhD, MD Pfizer Japan Inc, Japan
Michel Grothe PhD DZNE, German Center for Neurodegenerative Diseases,
Rostock, Germany
Ibrahim Hakan Gürvit MD Department of Neurology, Istanbul University
Faculty of Medicine, Istanbul, Turkey
Spencer Guthrie MBA, PMP Genentech, Elan, Jansen Alzheimer's
Immunotherapy and Ultragenyx Pharmaceutical, Novato, California, USA
Harald Hampel MA, MD, MSc Department of Psychiatry, University of
Frankfurt, Germany
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LIST OF CONTRIBUTORS
Lynne Hughes BMedSci, PhD, PMP Quintiles, Reading, Berkshire, UK
Michael Hüll University of Freiburg Medical School, Freiburg, Germany
Hilal İlbars PhD Turkish Medicines and Medical Devices Agency, Ankara, Turkey
Takeshi Iwatsubo MD, PhD Department of Neuropathology and Neuroscience,
University of Tokyo, Japan
Roy W. Jones BSc, FRCP, DipPharmMed Research Institute for the Care of
Older People, Royal United Hospital, Bath, and University of Bath, Bath, UK
Nadina C. Jose MD Anidan Group Pte Ltd, Singapore
Amir Kalali Quntiles Inc, USA
Seong Yoon Kim MD, PhD Department of Psychiatry, Asan Medical Center,
University of Ulsan, Seoul, Korea
Miia Kivipelto MD, PhD Karolinska Institute, Gävlegatan, Stockholm, Sweden
Amos D. Korczyn MD, MSc Tel Aviv University, Ramat Aviv, Israel
Bernd J. Krause MD Department of Nuclear Medicine, University of Rostock,
Germany
Jens Kurth Department of Nuclear Medicine, University of Rostock, Germany
Huafang Li MD, PhD Shanghai Mental Health Center, Shanghai, China
Francesca Mangialasche MD, PhD Aging Research Center, Karolinska
Institutet-Stockholm University, Stockholm, Sweden
Zeev Meiner MD Hadassah Hebrew-University Hospital, Jerusalem, Israel
Hans J. Möbius MD, PhD EnVivo International, Brunnen, The Netherlands
Ricardo Nitrini MD Department of Neurology, University of São Paulo School
of Medicine, Sao Pãulo, Brazil
Tiia Ngandu MD National Institute for Health and Welfare, Helsinki, Finland
Muriel O’Byrne PhD Elan Pharma International Ltd, Dublin, Ireland
Peter Schüler MD Global Medical and Safety Services, ICON Clinical Research,
Germany
Klaudius Siegfried PhD ICON Clinical Research, Germany
Sidney A. Spector MD VA Medical Center, Phoenix, Arizona, USA, and Global
Biopharma, Scottsdale, Arizona, USA
Stefan Teipel MD DZNE, German Center for Neurodegenerative Diseases,
Rostock, Germany and Department of Psychosomatic Medicine, University of
Rostock, Rostock, Germany
Yağiz Üresin MD Department of Pharmacology, Istanbul University Faculty of
Medicine, Istanbul, Turkey
Bruno Vellas MD, PhD University Hospital Center, Toulouse, France and
Clinical Nutrition Laboratory University of New Mexico, USA
Michael Weiner MD UCSF Professor of Medicine, Radiology, Psychiatry &
Neurology, University of California, California, USA
Jing Yin ICON Clinical Research Pte Ltd, Singapore
Xue (Kate) Zhong MD Cleveland Clinic Lou Ruvo Center for Brain Health, Las
Vegas, Nevada, USA