Global Clinical Trials Playbook

Capacity and Capability Building

Menghis Bairu, Richard Chin

• Publisher: Academic Press
• Year: 2012
• ISBN:
  9780124158603
• Topic: Medicine
• Subtopic: Pharmacology

Pharmaceuticals companies, biotech companies, and CROs, regardless of size, all face the same challenge of managing costs and operational execution associated with bringing a valuable drugs and devices to market. Because of timeline pressures and cost as well as the growing interest in "neglected diseases" and diseases affecting the emerging nations, clinical trials are increasingly conducted in emerging markets and developing countries where infrastructure, leadership, skilled personnel and a governance are at a premium.

Working with academics, regulatory professionals, safety officers, experts from the pharma industry and CROs, the editors have put together this up-to-date, step-by-step guide book to building and enhancing global clinical trial capacity in emerging markets and developing countries. This book covers the design, conduct, and tools to build and/or enhance human capacity to execute such trials, appealing to individuals in health ministries, pharmaceutical companies, world health organizations, academia, industry, and non-governmental organizations (NGOs) who are managing global clinical trials.

• Gives medical professionals the business tools needed to effectively execute clinical trials throughout the world
• Provides real world international examples which illustrate the practical translation of principles
• Includes forms, templates, and additional references for standardization in a number of global scenarios

Section 1

Clinical Trials

Chapter 1 Introduction

Chapter 2 Global Clinical Trials

Chapter 3 Building a Healthy Mechanism for Good Clinical Practice-Compliant Global Trials

Chapter 4 Clinical Trial Sites Capabilities

Chapter 5 How to Select and Oversee Contract Research Organizations

Chapter 6 The How-To of Global Clinical Trial Forecasting, Budgeting, and Project Management

Chapter 1

Introduction

Menghis Bairu

Elan Biopharmaceuticals, San Francisco, California, USA

Wherever in the world we stand, the majority of clinical trials are being conducted somewhere else in the world, under a different regulatory framework and in different cultural settings. However, we all rely on the same trials to make decisions; as regulators, to allow or disallow marketing authorizations, and, as patients and healthcare providers, to use or not to use a medicine.

Fergus Sweeney, Head of Inspections at the European Medicines Agency (September 2010)

Thirty years ago, the United States Food and Drug Administration (FDA) formalized a process for the inclusion of data derived from clinical trials conducted overseas that could be included in a new drug application (NDA) submitted for marketing approval by pharmaceutical sponsors. The impetus for this new FDA guideline derived from clinical trials being sponsored by US government agencies, academic research medical centers, and US pharmaceutical companies which were being conducted outside the USA. At that time, 41 foreign clinical investigators were conducting drug research under an investigational new drug application. By 1999, over 4400 foreign investigators were participating in US-sponsored research, and by 2008, more than 200,000 patients were enrolled in over 6500 research sites outside the USA for over 80 percent of the NDAs submitted to the FDA that year.

This trend in globalization of clinical trial research was by no means limited to regulatory submissions in the USA. During the years 2005–2009, registration studies submitted to the European Medicines Agency (EMA) involved more than 44,000 investigator sites in 89 countries. Only 38.8 percent of patients within the European Union or European Economic Area were enrolled in studies sponsored by local institutions. The remainder of patients were recruited offshore.

The forces that have driven the globalization of clinical trial research are multifactorial, with potential benefit for patients, sponsors, local communities, and foreign governments. Government-, non-government-, and pharmaceutical industry-sponsored research conducted in emerging nations reflects the desire to study medicines in populations with locally endemic diseases and infections which may also be found in developed countries. In addition, for pharmaceutical companies that anticipate selling in key global markets, the impetus to use overseas study sites undoubtedly reflects the potential to reduce operational costs and recruit larger numbers of drug-naïve patients over shorter periods, while establishing a research and marketing presence in these developing countries.

Nevertheless, the globalization of clinical trial research has revealed significant challenges, especially in developing countries, with regard to understanding good clinical practice, informed consent, patient safety, ethics review capacity, access to medical equipment, integrity of acquired data, and regulatory oversight. Low- and middle-income countries in which clinical trials are conducted vary substantially in the extent of their capabilities and experience with clinical trial research. Many developing countries have limited or no institutional regulatory infrastructure and ethics review boards to oversee the conduct of clinical trials at globally accepted standards. Local clinical investigators have varying degrees of skill, training, and experience requisite to supervise the conduct of a clinical trial. The extent of understanding and sophistication of patients, coupled with local cultural idiosyncrasies, affects informed consent, study participation, and overall expectations.

Recognition of these challenges over the past decade has led to a variety of publications, workshops, training programs, and guidelines in an effort to enhance the quality of the clinical trial enterprise in developing countries. Key stakeholders, including regulatory agencies in developed nations, the Word Health Organization (WHO), ministries of health, academia, the pharmaceutical industry, non-governmental organizations (NGOs), contract research organizations (CROs), and non-profit foundations, have forged a variety of partnerships to advance the quality of clinical research. For example, the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) was organized in 2001 “… to develop competent, independent, in-country decision making for promoting responsible conduct of human research and to monitor the quality and effectiveness of ethical review worldwide, with mutual understanding and respect for cultural, regional and national differences”. The European and Developing Countries Clinical Trials Partnership (EDCTP) was created in 2003 “… to accelerate the development of new or improved drugs, vaccines, microbicides and diagnostics against HIV/AIDS, malaria and tuberculosis, with a focus on phase II and III clinical trials in sub-Saharan Africa”. The US FDA holds ongoing training programs such as “Train the Trainer Good Clinical Practices”, to enhance the regulatory oversight of clinical trials in various regions around the world. Although these examples illustrate the enormous strides that have been taken to improve the quality of clinical trials conducted in developing nations, there has yet to be the consolidation of best practices regarding the various components of the clinical research enterprise that may be resourced for establishing high-quality clinical research institutions.

This book was written to provide resources under one cover which elucidate the various elements required for the successful implementation of clinical trials in developing countries. For the first time, the reader has a practical manual for developing and enhancing the infrastructure and processes required to conduct clinical research in developing countries. This book is divided into eight sections addressing the essential aspects of how to build and enhance global clinical trials capacity in emerging markets and developing countries. In Section 1, an introduction to the subject of global clinical trials is provided, with a focus on design and planning. The African perspective of appropriate and necessary training in good clinical practice of all personnel involved in conducting clinical trials, in both urban and rural locales in African countries, is discussed. Clinical trial site capabilities and the importance of establishing adequate standard operating procedures in sub-Saharan Africa are discussed, while addressing the challenges of informed consent, clinical execution by principal investigators and staff, partnering with local pharmacy, and processing of laboratory specimens, practices that should be intended to endure from trial to trial. Building and strengthening clinical trial site capabilities and capacity in other developing/emerging markets, including India, China, Eastern Europe, Singapore, and Turkey, are covered in Section 2. Partnering with the right contract research organization is a vital component in conducting a successful clinical trial; the different perspectives of working with global and niche CROs and the options available for choosing a CRO when conducting an overseas clinical trial are presented. The final chapters of this section provide the reader with guidelines for prioritizing clinical trial research based on national interests, as well as addressing the management of resources, budgets, and personnel, with an emphasis on future planning to sustain the clinical research enterprise locally.

Section 3 provides a roadmap for local regulatory agencies to build and enhance their capacity to evaluate investigative new drug and NDA applications, with recommendations of best practices to develop the regulatory capacity for the monitoring, oversight, enforcement, and approval of clinical trials. Section 4 addresses the establishment of infrastructure, operating procedures, and personnel training for pharmacovigilance and risk management by local government agencies.

The challenges and opportunities for outsourcing of electronic data collection and data management in developing countries, with examples of best practices for minimizing data dilution, are presented in Section 5. Section 6 contains a chapter dealing with the important concept of the establishment and maintenance of highly functioning investigational review boards, with special consideration of vulnerable populations in developing nations. The critical importance of identifying local talent, optimizing recruitment and retention of staff to ensure continuity during a clinical trial and from trial to trial, and the means for ensuring the protection of intellectual property are also discussed. Section 7 addresses best practices and challenges for acquiring and managing clinical data of high quality through strategic planning, and the process and preparation for external monitoring by sponsors and regulatory agencies. Finally, in Section 8 (Appendices), samples of study protocol, a consent form, job descriptions, case report forms, and a statistical analysis plan, as well as the International Committee on Harmonisation (ICH) guidelines, are provided.

This book is the first of its kind to provide guidelines and best practices to the reader for enhancing the capacity of developing countries to participate in clinical trial research at the highest level. As a complement to the recently published Global Clinical Trials: Effective Implementation and Management by the same authors, this book is aimed at individuals in the WHO, ministries of health, pharmaceutical companies, clinical researchers in academia, non-profit organizations such as the Bill and Melinda Gates Foundation, the World Bank, and NGOs who are involved in clinical research around the world, and will serve as a vital reference for anyone interested in building and enhancing clinical and research capacity in developing countries.

Chapter 2

Global Clinical Trials: Study Design and Planning

Richard Chin

UCSF School of Medicine, San Francisco, California, USA

Chapter Outline

Introduction

Prin...

Table of contents

• Cover image
• Title page
• Contents
• Dedication
• Copyright
• International Editorial Advisors
• Contributors
• Section 1 Clinical Trials
• Section 2 Strengthening and Building Clinical Trial Site Capabilities and Capacity in Developing and Emerging Markets
• Section 3 Regulatory Capacity
• Section 4 How to Build and Enhance Pharmacovigilance and Risk Management Capacity and Capability
• Section 5 Electronic Data Capture
• Section 6 Ethics, Human Resources, and Intellectual Property
• Section 7 Quality Assurance and Data Management
• Section 8 Appendices
• Index
• Color Plates