The Fundamentals of Clinical Research. P. Michael Dubinsky

that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).The IRB/IEC, investigator, and sponsor have responsibilities to ensure the protection of information that may identify research subjects (e.g., name, contact information, initials) in order to respect their privacy. IRBs/IECs and local regulatory requirements may dictate which, if any, personal identification for subjects may be used in trial data and documentation and with whom their personal information may be shared. Investigators and sponsors will implement procedures to ensure that unauthorized subject personal identification are not released and shared intentionally or inadvertently. (Chapter 19 Informed Consent and Other Human Subject Protection; Chapter 21 Safety Monitoring and Reporting; Chapter 22 Monitoring Overview).

      12 2.12 Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.The sponsor will ensure that investigational products are manufactured, handled, and stored according to GMP. The sponsor will implement procedures for product handling, storage, and shipping from the distribution facility to investigators and for return, receipt, and destruction to the facility. The investigator will implement procedures for receipt, handling, storage, administration to subjects, and destruction or return of investigational product to the sponsor. The sponsor will also implement procedures to monitor the entire 'chain of custody' of the investigational products to ensure compliance with the protocol and applicable regulatory requirements. (Chapter 17 The Investigational Product (Clinical Supplies); Chapter 21 Safety Monitoring and Reporting; Chapter 22 Monitoring Overview).

      13 2.13 Systems with procedures that assure the quality of every aspect of the trial should be implemented.All players, the IRB/IEC, investigator (and third parties), and sponsor (and CROs), will implement procedures that assure the quality of every aspect of the trial. Quality procedures include procedures for quality assurance and quality control, including establishing SOPs, training procedures, monitoring procedures, audit programs, ongoing quality control checks, and risk assessment and mitigation methods. (Source: ICH [1] Section on Quality in Clinical Trials).

6.5 Summary

      The ICH E6(R2) presents a set of international ethical and scientific quality standard for designing, conducting, recording, and reporting trials that involve the participation of human subjects (ICH E6(R2) Introduction). The Guideline includes principles that lay the foundation for the responsibilities and operational standards of GCP. It is important to understand the application of principles to guide the behavior and chain of reasoning for all who are involved in the conception, planning, and execution of a clinical trial in order to protect human subjects and ensure the integrity of trial data.

      Knowledge Check Questions

      1 What is the definition of GCP?

      2 What are the 13 principles of GCP?

      3 How does each of the 13 principles of GCP apply to clinical research?

      4 Overheard:“What is GCP?”Sponsor's associate responsible for filing documents in the trial master file.Comment and discuss:Why does the individual in this role need to know GCP?What aspect(s) of GCP would apply to his/her role?

Reference

      1 1 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Integrated Addendum to ICH E6(R1):Guideline for Good Clinical Practice, E6(R2) (2016). Current Step 4 version dated 9 November 2016. https://www.ich.org/page/efficacy‐guidelines

7 Players Roles and Responsibilities Overview

       Karen A. Henry

      GCP Key Point

       Clinical trials should be conducted in accordance with GCP and the applicable regulatory requirement(s).

7.1 Introduction

      Who are the main players involved in the conduct of clinical research? To answer this question, let us first look at the reason clinical trials exist.

      As we learned from the history of the evolution of clinical trials and drug development, there were incidents where many people were seriously or fatally harmed from using “medicinal” products that were sold on the market. The ensuing public outcry was heard by the government, and legislators created laws that evolved to ultimately require that a medicinal product must be proven to be safe and effective before it can be sold in the market place. (Chapter 1 Good Clinical Practice History)

Until a medicinal product is proven to be safe and effective, the product would be identified as “investigational.” The laws also state that the entity to decide if a product is safe and effective would be a representative of the government and that the method for first proving that a product is safe and effective would be through the conduct of a series of well‐controlled experiments, including trials on human subjects; hence, the requirement for clinical trials. The regulatory authorities established specific rules, regulations, and guidelines regarding clinical research for investigational products. The main players involved in clinical research conduct were identified as the Sponsor, Clinical Investigator, Institutional Review Board (IRB) or Independent Ethics Committee (IEC), the research participant, and the Regulatory Authority. The ICH E6(R2) guidance for Good Clinical Practice provides a unified standard for the generation of such clinical trial data that are intended to be submitted to regulatory authorities (ICH E6(R2) Introduction [1]).

      ICH GCP Guidelines define roles and responsibilities for each player involved in the planning, executing, and reporting of a clinical trial: IRB/IEC, investigator, sponsor/CRO, regulatory agency, and research participant. This chapter will define the different types of players and describe their roles and interaction in clinical research. The details of each player's responsibilities are provided in the respective chapters for IRB/IEC (Chapter 8), investigator and sponsor (Chapter 9), the research volunteer (Chapter 10), and the regulatory authority (Chapter 11).

7.2 Objectives

      In this chapter topic we will answer the following questions:

      1 Who are the main players involved in the conduct of clinical research?

      2 How do the main players interact with each other in the clinical research arena?

      7.2.1 Main Players Involved in the Conduct of a Clinical Trial

      The main players involved in the conduct of a clinical trial are: Sponsor, Investigator, IRB/IEC, Regulatory Authority, and Research Participant (Plate 3).

      7.2.1.1 The Sponsor

      The Sponsor is the “owner” of an investigational product. The sponsor is interested in studying