Good Clinical Practice: A Question & Answer Reference Guide - May 2012 - (Page 1)

Introduction At its core, good clinical practice (GCP) is a set of broad regulatory requirements, standards, and recommendations that apply to thousands of highly specific tasks, processes, and roles in the conduct of clinical research. Much of the GCP practices and requirements are derived from FDA’s long history in this area. Given the disparity between the detailed nature of clinical trial processes and tasks and the general GCP requirements and standards under which they occur, it is not surprising that interpreting and implementing GCP standards continue to represent challenges for the pharmaceutical, biotechnology, and medical device industries. It is important to remember that much of the practical standards used in the conduct of clinical trials are “best practices” derived from regulations, guidance, and industry standards and practices, and are not all found in black and white in the regulations. As is true of any area in which interpretation plays such a central role, the GCP discipline is today, as much as it has ever been, characterized by many long-standing and emerging questions regarding how broad GCP standards should be applied in the real world of clinical trials. Today, emerging questions in such areas as global clinical trial standards, social media, pharmacogenomic testing, conflict-of-interest disclosures, Part 11, and electronic clinical trials, as well as the Privacy Rule and its implications for clinical research, are taking their places aside longstanding GCP gray areas, including how FDA GCP standards intersect with ICH GCP principles and the federal government’s Common Rule. Recognizing this, we set out to systematically collect, catalog, and answer the most important, emerging, and difficult questions regarding the interpretation and implementation of GCP standards today. In doing so, it is our hope that the resultant work, Good Clinical Practice: A Question & Answer Reference Guide 2012 (Tenth Edition), will represent the next step in GCP training and instruction—one that begins where all others leave off. Through this text’s question-and-answer format, we attempt to highlight, explore, and address a vast array of GCP-related questions, some of which have persisted for many years without definitive answers, and some of which have emerged in response to new clinical trials- or regulatory-related developments. Our newly revised and expanded tenth edition includes many new questions and answers, addressing emerging areas such as FDA’s new “Draft Reflection Paper on Risk-Based Quality Management in Clinical Trials”; FDA’s proposed changes to HIPAA regulatory requirements, “Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators”; questions arising from the HITECH Rule and research activities; new FDA compliance initiatives, priorities, statistics, and trends; and more than 100 questions and answers on informed consent alone. The 2012 edition also includes vastly expanded and updated GCP and clinical trial standards in Latin America and China, and an entirely new section on GCP regulations and guidelines in Ukraine. In creating this work, over a dozen contributing authors selected a few hundred questions culled from a much larger list developed with the help of more than 100 industry and FDA experts, ranging from clinical research associates to QA auditors, from clinical trainers to regulatory attorneys, and from study investigators/coordinators to FDA field inspectors. In addressing these questions, we had one clear and overriding goal: to provide definitive answers where they exist, and to provide informed, thoughtful, and well-researched answers where they do not. In developing these answers, we called upon our own experiences in clinical research, reviewed hundreds of regulatory documents, and consulted directly with dozens of FDA officials and a network of colleagues, opinion leaders, attorneys, and clinical researchers. In developing the new tenth edition, we have once again acknowledged the global nature of today’s clinical trial enterprise by inclduing chapters on GCP and clinical research standards in foreign countries and regions. In one of our two international chapters, we update and expand our questions regarding the implementation and interpretation of GCPs in the European Union. In the other, we address GCP-related questions and issues in several additional regions that are becoming increasingly important in global clinical trial programs. We have also updated our section that features complete metrics and analyses on GCP and clinical trial compliance trends. We have developed the answers in this reference guide to reflect the multiple layers of standards that may be applied under GCP. In many areas, for example, emerging industry “best practice” standards or international standards (e.g., ICH) may surpass those mandated or recommended by FDA GCP. We ask that, in using this text, readers keep in mind that many areas lack an absolute consensus in approach, and that there is no perfect knowledge in the GCP discipline. After all, GCP is a complicated, evolving discipline 1

Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2012

Good Clinical Practice: A Question & Answer Reference Guide - May 2012
Table of Contents
Introduction
Section 1: GCP Regulations, Standards and Guidelines for Clinical Research
Section 2: Investigators/Sites
Section 3: Form FDA-1572/Statement of the Investigator
Section 4: Study Sponsors and Clinical Trial Monitoring
Section 5: Informed Consent
Section 6: Source Data/Documentation
Section 7: Clinical Trial Protocols/Protocol Changes/Protocol Violations
Section 8: Institutional Review Boards
Section 9: Drug/Study Safety and Safety Reporting
Section 10: FDA Inspections, Quality Assurance Activities, and Study Auditing
Section 11: Computerized Systems, e-Clinical Trials, and Electronic Records Rules
Section 12: Patient Recruitment
Section 13: Conflicts of Interest/Financial Disclosure
Section 14: The HIPAA Privacy Rule and FDA-Regulated Clinical Trials
Section 15: Drug Accountability, Administration, and Labeling
Section 16: Fraud, Negligence, and Regulatory Non-Compliance
Section 17: Subject Diaries
Section 18: GCP and Clinical Research Standards in the European Union and An Interview with Fergus Sweeney, Ph.D., EMA Head of Sector, Compliance and Inspection
Section 19: Clinical Trial and GCP Standards in Selected Leading Countries/Regions: Latin America, China, Russia, Ukraine, and India
Section 20: GCP Compliance Statistics and Trends
21 CFR Part 11 — Electronic Records; Electronic Signatures
21 CFR Part 50 — Protection of Human Subjects
21 CFR Part 54 — Financial Disclosure by Clinical Investigators
21 CFR Part 56 — Institutional Review Boards
21 CFR Part 312 — Investigational New Drug Application
ICH Consolidated Guideline on Good Clinical Practice (E6)
ICH Guideline on Clinical Safety Data Management (E2A)
European Union Clinical Trials Directive
European Union Good Clinical Practice Directive

Good Clinical Practice: A Question & Answer Reference Guide - May 2012