Clinical Trials Handbook
Pharmaceutical Development Series

Best practices for conducting effective and safe clinical trials

Clinical trials are arguably the most important steps in proving drug effectiveness and safety for public use. They require intensive planning and organization and involve a wide range of disciplines: data management, biostatistics, pharmacology, toxicology, modeling and simulation, regulatory monitoring, ethics, and particular issues for given disease areas. Clinical Trials Handbook provides a comprehensive and thorough reference on the basics and practices of clinical trials.

With contributions from a range of international authors, the book takes the reader through each trial phase, technique, and issue. Chapters cover every key aspect of preparing and conducting clinical trials, including:

• Interdisciplinary topics that have to be coordinated for a successful clinical trialData management (and adverse event reporting systems)
• Biostatistics, pharmacology, and toxicology
• Modeling and simulation
• Regulatory monitoring and ethics
• Particular issues for given disease areas-cardiology, oncology, cognitive, dementia, dermatology, neuroscience, and more

With unique information on such current issues as adverse event reporting (AER) systems, adaptive trial designs, and crossover trial designs, Clinical Trials Handbook will be a ready reference for pharmaceutical scientists, statisticians, researchers, and the many other professionals involved in drug development.

Preface.

1 Introduction to Clinical Trials (John Goffin).

2 Regulatory Requirements for Investigational New Drug (Venkat Rao).

3 Preclinical Assessment of Safety in Human Subjects (Nancy Wintering and Andrew B. Newberg).

4 Predicting human adverse drug reactions from non-clinical safety studies (Jean-Pierre Valentin, Marianne Keisu & Tim G. Hammond).

5.1 History of Clinical Trial Development and the Pharmaceutical Industry (Jeffery Peppercorn and Thomas Roberts).

5.2 Adaptive Research (Michael Rosenberg).

6 Organization and Planning (Sheila Sprague and Mohit Bhandari).

7 The Process of Data Management (Nina Trocky and Cynthia Barndt).

8 Clinical Trials Data Management (Eugenio Santoro and Angelo Tinazzi).

9.1 Clinical Trials and the FDA (Tarek M. Mahfouz and Janelle S. Crossgrove).

9.2 Phase I Clinical Trials (Shayne Gad).

9.3 Phase II Clinical Trials (Say-Beng Tan and David Machin).

9.4 Designing and Conducting Phase III Studies (Nabil Saba, M.D., John Kauh, M.D., and Dong M. Shin, M.D.).

9.5 Phase IV (Karl Wegscheider).

9.6 Phase IV and Post Marketing Clinical Trials (Ali Miraj Khan).

9.7 Regulatory Approval (Fred Henry and Weichung J. Shih).

9.8 A New Paradigm for Analyzing Adverse Drug Events (Ana Szarfman, Jonathan G. Levine, and Joseph M. Tonning).

10.1 Clinical Trials in Interventional Cardiology: Focus on the XIENCE Drug-Eluting Stent (Doostzadeh J, Bezenek S, Cheong W-F, Sood P, Schwartz L, Sudhir K).

10.2 Clinical Trials Involving Oral Diseases (Bruce L Pihlstrom, Bryan Michalowicz, Jane Atkinson and Albert Kingman).

10.3 Dermatology Clinical Trials (Maryanne Kazanis, Alicia Van Cott, Alexa Boer Kimball).

10.4 Emergency Clinical Trials (Joaquin Borras-Blasco, Andres Navarro-Ruiz and Consuelo Borras).

10.5 Gastroenterology (Lise Lotte Gluud and Jorgen Rask-Madsen).

10.6 Gynaecology Randomised Control Trials (Khalid Khan).

10.7 Special Population Studies (Healthy Patient Studies) (Doris K. Weilert).

10.8 Musculoskeletal (Masami Akai).

10.9 Oncology (Matjaz Zwitter).

10.10 Pharmacological Treatment Options for Non-exudative and exudative age-related macular degeneration (Alejandro Oliver, Thomas Ciulla, and Alon Harris).

10.11 Paediatrics (Anne Cusick, Natasha Lannin & Iona Novak).

10.12 Dementia (Encarnita Raya-Ampil and Jeffrey Cummings).

10.13 Clinical Trials in Urology (Geoffrey R Wignall, Carol Wernecke, Linda Nott & Hassan Razvi).

10.14 Clinical Trials on Cognitive Drugs (Elisabetta Farina and Francesca Baglio).

10.15 Bridging Studies in Pharmaceutical Safety Assessment (Jon Ruckle).

10.16 A Brief History of Clinical Trials on Vaccines (Megan J. Brooks, Joseph J. Sasadeusz, and Gregory A. Tannock).

11 Methods of Randomization (Gladys McPherson and Marion Campbell).

12 Randomized Controlled Trials (Giuseppe Garcea and David P. Berry).

13 Cross-Over Designs (Raphael Porcher and Sylvie Chevret).

14.1 Biomarkers (Michael R. Bleavins, Claudio Carini, Malle Jurima-Romet, and Ramin Rahbari).

14.2 Biomarkers in clinical drug development: parallel analysis of Alzheimer Disease and Multiple Sclerosis (Christine BETARD, Filippo MARTINELLI BONESCHI & Paulo CARAMELLI).

15 Review Boards (Maureen Hood, Jason Kaar, and Vincent Ho).

16 Size of Clinical Trials (Jitendra Ganju).

17 Blinding and Placebo (Artur Bauhofer).

18 Pharmacology (Thierry Buclin).

19 Modeling and Simulation in Clinical Drug Development (Jerry Nedelman, Frank Bretz, Roland Fisch, Anna Georgieva, Chyi-Hung Hsu, Joseph Kahn, Ryosei Kawai, Phil Lowe, Jeff Maca, Jose’ Pinheiro, Anthony Rossini, Heinz Schmidli, Jean-Louis Steimer, Jing Yu).

20 Monitoring (Nigel Stallard and Susan Todd).

21 Inference Following a Sequential Clinical Trial (Aiyi Liu and Kai F. Yu).

22 Statistical methods for Analysis of Clinical Trials (Duolao Wang, Ameet Bakhai, and Nicola Maffulli).

23 Explanatory and Pragmatic Clinical Trials (Rob Herbert).

24.1 Ethics of Clinical Research in Durg Trials (Roy G. Beran).

24.2 Ethical Issues in Clinical Research (Kelton Tremellen and David Belford).

25 Regulations (Ramzi Dagher, Rajeshwari Sridhara, Nallaperumal Chidambaram, and Brian P. Booth).

26 Future Challenges in the Design and Ethics of Clinical Trials (Carl-Fredrik Burman and Axel Carlberg).

27 Proof-of-Principle/Proof-of-Concept trials in Drug Development (Ayman Al-Shurbaji).

Shayne Cox Gad, PhD, DABT, ATS, is the Principal of Gad Consulting Services. Dr. Gad has more than thirty years of experience as a toxicologist, statistical consultant, manager, and general consultant on research and development in the chemical, consumer product, contract testing, biotechnology, medical device, and pharmaceutical industries. He is the author of thirty-nine books and numerous papers, presentations, and other publications.