Global Clinical Trials

Effective Implementation and Management

Richard Chin, Menghis Bairu

• Publisher: Academic Press
• Year: 2011
• Print ISBN: 9780123815378
• eBook ISBN: 9780123815385
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

This book will explore the great opportunities and challenges which exist in conducting clinical trials in developing countries. By exploring the various regulations specific to the major players and providing insight into the logistical challenges including language barriers, this book provides a working tool for clinical researchers and administrators to navigate the intricacies of clinical trials in developing countries. Important topics such as ethical issues will be handled very carefully to highlight the significant differences of conducting this work in various jurisdictions. Overall, it will present a clear and comprehensive guide to the ins-and-outs of clinical trials in various countries to assist in design, development, and effectiveness of these trials.- Contributors include high-profile, respected figures who have paved the way for clinical trials in developing countries- Provides hands-on tools for regulatory and legal requirements and qualification, design, management, and reporting- Case studies outline successes, failures, lessons learned and prospects for future collaboration- Includes country-specific guidelines for the most utilized countries- Foreword by David Feigel, former Head of CDRH at FDA

Chapter 1. Background

Richard Chin

Institute for OneWorld Health, South San Francisco, CA, USA

Contents

1.1. Introduction3

1.2. Growth of Global Clinical Trials4

1.3. Drivers of Globalization6

1.4. Issues of Globalization7

1.5. Control and Inspections of Foreign Sites8

1.6. Ethnic and Genetic Differences8

1.7. Usability of International Clinical Data in Regulatory Filings9

1.8. World Health Organization Prequalification Process12

1.8.1. History of Prequalification12

1.8.2. Prequalification Process for Drugs13

1.8.3. Prequalification Process for Vaccines15

References17

There has been a rapid increase in the globalization of clinical trials. The proportion of clinical studies being conducted across the world, especially in developing countries, has been driven by the need for lower cost, greater speed, and higher quality. This book is a comprehensive survey of the state of global clinical trials.

1.1. Introduction

Not since almost a century and a half ago, when the modern economy was created by a confluence of new inventions – telegraph, railroad, refined oil, and Bessemer steel – have we seen the wholesale transformation of entire industries that we are seeing today. Propelled by the Internet, microprocessors, mobile phones, and standardized shipping containers, the world has over the last decade or so been fast-forwarding into globalization with a rapidity and scale that is hardly imaginable.

As with other industries such as information technology and traditional manufacturing, drug development has become highly globalized. Globalization brings both significant benefits and potential difficulties. Done correctly, global clinical trials lower the cost of drugs for everyone, distribute modern science and medicine broadly, and enhance the health of patients around the world. However, the endeavor of drug development is complicated and risky, and it is extremely important to conduct trials correctly. The goal of this book is to help physicians and clinical trial professionals everywhere to achieve that objective.

1.2. Growth of Global Clinical Trials

The number of international trials has been growing rapidly. According to a report from the Office of the Inspector General (OIG), as of 2008, 80 percent of marketing applications for drugs and biologicals approved by the US Food and Drug Administration (FDA) contained data from US clinical trials conducted outside the USA [1]. Table 1.1 shows the breakdown from the report [1]. According to the same source, over half of the sites and subjects in these applications were from non-US sources.

Table 1.1 Food and Drug Administration (FDA) marketing approval for drugs and biologicals containing clinical data approved in fiscal year 2008
Source: OIG analysis of FDA marketing applications approved in fiscal year 2008.

These numbers are based on 121 applications with sufficient information to determine whether the data were non-US or US.
Marketing applications	Drugs	Biologicals	Drugs and biologicals
Applications with only US data	15	9	24
Applications with non-US and US data	82	5	87
Applications with only non-US data	9	1	10
Totals	106	15	121

As can be seen in Table 1.2, 57 percent of patients in new drug applications (NDAs) and 87 percent of patients in biologicals license applications (BLAs) were from non-US sites. The largest proportion of non-US patients came from Western Europe, as of 2008 approvals (Figure 1.1) [1]. Figure 1.1 is based on patients in approved applications, and therefore reflects the proportion of patients enrolled into trials over the past 10 years or so.

Table 1.2 Number and percentage of non-US subjects and sites from clinical trials supporting drug- and biological-marketing applications approved in fiscal year 2008
Source: OIG analysis of FDA marketing applications approved in fiscal year 2008.

These numbers are based on data from 193 clinical trials with complete subject and site information.
	Drugs	Biologicals	Drugs and biologicals
No. of non-US and US subjects	92.859	206,842	299,701
No. of non-US subjects	52.820	179,712	232,532
Percentage of non-US subjects	56.9%	86.9%	77.6%
No. of non-US and US trial sites	11,227	717	11,944
No. of non-US trial sites	6,129	356	6,485
Percentage of non-US trial sites	54.6%	49.7%	54.3%

Figure 1.1 Percentage of non-US clinical trial subjects and sites by region for FDA marketing applications approved in fiscal year 2008. These numbers are based on data from 193 clinical trials with complete subject and site information. Source: OIG analysis of FDA marketing applications approved in fiscal year 2008.

The proportion of non-US patients is growing rapidly (Figure 1.2) [1]. This trend is not confined to lower quality or less prominent clinical trials. An analysis by Glickman and colleagues recently found that between 1995 and 2005, the number of countries represented in a sample of studies published in the New England Journal of Medicine doubled from 33/150 to 70/150 [2].

Figure 1.2 Trend in non-US clinical investigators as a percentage of all clinical investigators identified in investigational new drug (IND) applications from 1998 to 2008.

These figures are largely consistent with the numbers calculated by Tufts Center for Drug Development, which estimates that in 2007, 57 percent of the patients in clinical trials came from the USA, 14 percent from Western Europe, and 29 percent from rest of the world.

1.3. Drivers of Globalization

The trend toward globalization has been fueled by several factors. The rapidly increasing cost of clinical trials – increasing at 20 percent per year – has been driving much of the effort. Conducting clinical trials in developing countries can easily reduce costs by 50 percent or more, and in some cases can reduce costs by up to 90 percent.

More importantly, recruitment of patients tends to be much faster in developing countries. In many cases, recruitment can be increased by 100 percent, and in some cases by 500 percent or more. In an industry such as pharmaceutical development, speed of enrollment can be a very strong driver for globalization.

In addition, in some diseases such as oncology and rheumatology, it can be difficult to recruit patients who are naïve to therapy into clinical trials in developed countries. In the USA and Europe, for example, most patients with severe rheumatoid arthritis may already have been exposed to biologicals such tumor necrosis factor (TNF) inhibitors. It can be almost impossible to enroll patients who are TNF inhibitor naïve into clinical trials in those countries. Developing countries can offer a larger pool of treatment-naïve patients.

In other cases, the diseases of interest only exist in those countries, or the prevalence is much higher in those countries. Certain forms of hepatitis are one example. Global health has become an important area of drug development, largely owing to the investment by ...

Table of contents

• Cover image
• Table of Contents
• Dedication
• Front Matter
• Copyright
• About the Editors
• Foreword
• Contributors
• Chapter 1. Background
• Chapter 2. Bioethical Considerations in Global Clinical Trials
• Chapter 3. United States Regulations
• Chapter 4. European Union Regulations
• Chapter 5. Japanese Regulations
• Chapter 6. Indian Regulatory Framework
• Chapter 7. Clinical Trials in India
• Chapter 8. Chinese Regulatory Framework
• Chapter 9. Clinical Trials in China
• Chapter 10. Clinical Trials in Taiwan
• Chapter 11. Clinical Trials in the Philippines
• Chapter 12. Clinical Trials in the Middle East and North Africa
• Chapter 13. Clinical Trials in South Africa
• Chapter 14. Clinical Trials in Latin America
• Chapter 15. Clinical Trials in Central and Eastern Europe
• Chapter 16. Design of Clinical Trials for Emerging Countries
• Chapter 17. Study Management
• Chapter 18. Study Documents and Logistics
• Chapter 19. Clinical Study Conduct and Monitoring
• Chapter 20. Data Collection, Data Management, and Electronic Data Capture
• Colorplates
• Index