Good Clinical Practice: A Question & Answer Reference Guide - May 2012 - (Page 125)

Section 4: Study Sponsors and Clinical Trial Monitoring 4.1 Q. What is FDA’s new draft guidance on monitoring all about? A. In August 2011, the FDA issued a new draft guidance, “Guidance for Industry: Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring.” Although still a draft, the guidance is designed to make clear that sponsors can use a variety of approaches to fulfill their responsibilities related to monitoring investigator conduct and the progress of investigational new drug (IND) or investigational device exemption (IDE) studies. This guidance describes strategies for monitoring activities that reflect a modern, risk-based approach that focuses on critical study parameters and relies on a combination of monitoring activities to oversee a study effectively. For example, the guidance specifically encourages greater use of centralized monitoring methods where appropriate. In addition, the EMA issued a “Draft Reflection Paper on Risk-Based Quality Management in Clinical Trials” in August 2011. This draft guidance proposes consideration of a quality-based system for monitoring of clinical trials. It is similar in its proposals to the FDA draft guidance on risk-based monitoring. 4.2 Q. What happened to the original 1988 guidance on monitoring of clinical trials? A. This new guidance replaces the old 1988 guidance on monitoring of clinical trials. This guidance was withdrawn by FDA since it was no longer relevant or current. When the original guidance was written, it was before the implementation of email, the internet, electronic CRFs, and computerized systems used in clinical trials. 4.3 Q. For several years, FDA officials have spoken about the need to more closely study industry’s clinical monitoring practices and to address evolution in this area. Where does this stand today? A. Clearly, 2011 could be an inflection point for this area. Under the FDA/Duke-led Clinical Trials Transformation Initiative (CTTI) (see Q1.2), “clinical trial monitoring” was adopted as the very first “approved project concept”—a fact that program leaders attributed to “the growing concern about monitoring practices.” With the first work products for this project being released 2010—the first known survey to assess monitoring practices across trial settings and organization types (May 2010, Workstream 1) and a final report on the quality objectives of study monitoring (September 2010, Workstream 2)—the project appears headed for its final stages. In a September 2010 document, the FDA noted that, “the goal of this project is to identify best practices and develop sensible criteria to help sponsors choose the most appropriate monitoring methods for a trial, thereby improving quality while optimizing the deployment of resources… The next step is to evaluate the various practices’ strengths and weaknesses in meeting quality objectives over a range of clinical trial settings” (Workstream 3, see below). Monitoring Project Workstreams Workstream 1: Review of Current Practices. Characterized and described clinical monitoring methods currently used by 216 surveyed organizations (poster session released May 2010). Among its many findings, it concluded that onsite monitoring is routinely performed by industry and clinical research organizations (CRO), but less frequently and less extensively by academic/cooperative/government organizations. It also found that the scope of onsite monitoring visits varies by organization, with some procedures, source and regulatory documents reviewed more often by CROs and industry sponsors than by academic/cooperative/government organizations. Workstream 2: Definition of Key Quality Assurance Objectives (final report released September 2010). Identified the key quality assurance objectives (concentrating on those aspects that would materially affect the rights and well-being of the participants or the reliability of the study results, by considering the perspectives of prominent stakeholders (including regulators, participants, clinicians, trialists, academics, journal editors). The Workstream 2 findings largely confirmed the group’s “original assumptions—that the major quality objectives for monitoring of clinical trials are related to ensuring the integrity of data generated in clinical trials, and thus the reliability of the study findings, and ensuring that risks to human subjects are minimized and that subjects are treated fairly.” At an expert meeting in late 2009, an additional quality objective was emphasized—“that monitoring leads to quality 125

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