Clinical Trials in Older Adults

The concept of clinical trials in older adults is a relatively new field of research that is now rapidly expanding; with a need that is unmet there are currently no reference books specifically on this subject. A key question being asked by physicians about the worlds ageing population is whether an increase in life expectancy will be accompanied by a postponement of functional limitations and disability. Older subjects traditionally have limited involvement in mainstream clinical trials, even though research shows that they are more at risk from the adverse side effects of drugs.

Older adults have typically been excluded from mainstream clinical trials that test new medications and interventions. It is therefore critical that researchers begin systematically studying the effects of new therapies in older patients as our population ages.

Clinical Trials in Older Adults is the first book to consider the methodological issues underlying the evaluation of new treatments in older people:

Provides information on the methodology, monitoring and regulations for those planning to conduct clinical trials involving older adults Contains examples of ongoing and recently completed trials involving older adults Depicts how the issues regarding older adults in clinical trials could be properly addressed with the appropriate study design and conduct Identifies key issues in performing clinical trials in older patients with common geriatric conditions, i.e. Alzheimer s dementia, depression, low muscle mass, cancer
Physicians and researchers involved in clinical trials, regulators, members of ethical committees all need to have access to this key information.

Contributors vii

Preface xi

Part I: The frame

1 The exclusion of older subjects from clinical trials: the PREDICT study 3
Antonio Cherubini & Peter Crome

2 Clinical trials in older adults: a point of view from the industry 23
Susanna Del Signore & Philippe Guillet

3 Ethical issues in clinical trials involving older subjects: the right to participate in clinical trials and have access to care; the protection of vulnerable subjects and the issue of informed consent 45
Emmanuel Hirsch & Paul ]Loup Weil ]Dubuc

Part II: The implementation

4 Mastering the design of clinical trials for older persons: the tension between external validity and feasibility 63
Luigi Ferrucci & Stephanie Studenski

5 Pharmacokinetic and pharmacodynamic studies in older adults 79
Arduino A. Mangoni, Paul A.F. Jansen & Stephen H.D. Jackson

6 The role of comprehensive geriatric assessment (CGA) of older adults in clinical studies 95
Graziano Onder, Agnese Collamati, Andrea Poscia & Roberto Bernabei

7 Statistical issues in designing and interpreting clinical trials in older adults 107
Heather Allore, Mark A. Espeland & Michael E. Miller

Part III: The examples

8 Challenges in implementing large ]scale clinical trials in moderately functioning older adults 127
Stephen D. Anton, Sandrine Sourdet, Marco Pahor & Todd Manini

9 Clinical trials in Alzheimer s disease 153
Julien Delrieu & Bruno Vellas

10 Clinical trials in late ]life mood disorders 173
Lucio Ghio, Werner Natta, Marco Vaggi & Luigi Ferrannini

11 Clinical trials for conditions of low muscle mass and strength 197
Stephanie Studenski, Rosaly Correa–de–Araujo & Luigi Ferrucci

12 Clinical trials of cancer treatment in the elderly 219
Lodovico Balducci. Iordanis Gravanis & Francesco Pignatti

13 Clinical trials in nursing homes: challenges and practical solutions 231
Sandra Simmons, Barbara Resnick, John Schnelle & Joseph G. Ouslander

Index 255

Antonio Cherubini, is Director of Geriatrics and Geriatric Emergency Care at IRCCS–INRCA, Ancona, Italy. He is Associate Professor of Gerontology and Geriatrics at the Perugia University Medical School. He was research fellow at the department of Neurology, Massachusetts General Hospital, Harvard Medical School, from 1997–1998. He is co–author of several books of geriatric medicine in Italy. He is author of more than 200 papers in peer reviewed international journals. He is currently member of the Geriatric Expert Group of the European Medicine Agency.

Roberto Bernabei, Department of Gerontology and Geriatrics, Catholic University of Sacred Heart, Rome, Italy.

Luigi Ferrucci is the Scientific Director of the National Institute of Aging, NIH, Baltimore, MD, USA.

Niccolò Marchionni, Department of Critical Care Medicine and Surgery, Unit of Gerontology and Geriatric Medicine, University of Florence and Azienda Ospedaliero–Universitaria Careggi, Florence, Italy.

Bruno Vellas, Gerontopole de Toulouse. Department of Geriatric Medicine, Toulouse University Hospital, Toulouse; INSERM Unit 1027. University Toulouse III. Toulouse, France.

Stephanie Studenski, Professor of Medicine and Director of Research, Division of Geriatric Medicine, Program Director, Pittsburgh Pepper Center; Director, AOC in Geriatric Medicine, Staff Physician at the GRECC, VA Pittsburgh Healthcare System.